A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.
A class of compounds composed of repeating 5-carbon units of HEMITERPENES.
Cation-transporting proteins that utilize the energy of ATP hydrolysis for the transport of CALCIUM. They differ from CALCIUM CHANNELS which allow calcium to pass through a membrane without the use of energy.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Hydroquinones are chemical compounds that function as potent depigmenting agents, inhibiting the enzymatic conversion of tyrosine to melanin, used topically in the treatment of various dermatological disorders such as melasma, freckles, and hyperpigmentation.
Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES.
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
A fluorescent calcium chelating agent which is used to study intracellular calcium in tissues.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds.
A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.
Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes.
A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.
A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.
Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.
A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
Inorganic or organic compounds that contain boron as an integral part of the molecule.
Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
Intracellular receptors that bind to INOSITOL 1,4,5-TRISPHOSPHATE and play an important role in its intracellular signaling. Inositol 1,4,5-trisphosphate receptors are calcium channels that release CALCIUM in response to increased levels of inositol 1,4,5-trisphosphate in the CYTOPLASM.
The fluid inside CELLS.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A plant genus of the family APIACEAE. Members contain THAPSIGARGIN and other guaianolides (SESQUITERPENES, GUAIANOLIDE).
Cyclic compounds with a ring size of approximately 1-4 dozen atoms.
An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms.
A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.
A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
Unstable isotopes of calcium that decay or disintegrate emitting radiation. Ca atoms with atomic weights 39, 41, 45, 47, 49, and 50 are radioactive calcium isotopes.
The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
Established cell cultures that have the potential to propagate indefinitely.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.
The rate dynamics in chemical or physical systems.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.
An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
Compounds that bind to and activate PURINERGIC RECEPTORS.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The processes whereby the internal environment of an organism tends to remain balanced and stable.
Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
Gadolinium. An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
A proton ionophore that is commonly used as an uncoupling agent in biochemical studies.
Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.
An imidazole derivative that is commonly used as a topical antifungal agent.
Aniline compounds, also known as aromatic amines, are organic chemicals derived from aniline (aminobenzene), characterized by the substitution of hydrogen atoms in the benzene ring with amino groups (-NH2).
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.
An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.
An inorganic dye used in microscopy for differential staining and as a diagnostic reagent. In research this compound is used to study changes in cytoplasmic concentrations of calcium. Ruthenium red inhibits calcium transport through membrane channels.
A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.
Elements of limited time intervals, contributing to particular results or situations.

The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex. (1/2135)

When mammalian cells are subjected to calcium depletion stress or protein glycosylation block, the transcription of a family of glucose-regulated protein (GRP) genes encoding endoplasmic reticulum (ER) chaperones is induced to high levels. The consensus mammalian ER stress response element (ERSE) conserved among grp promoters consists of a tripartite structure CCAAT(N9)CCACG, with N being a strikingly GC-rich region of 9 bp. The ERSE, in duplicate copies, can confer full stress inducibility to a heterologous promoter in a sequence-specific but orientation-independent manner. In addition to CBF/NF-Y and YY1 binding to the CCAAT and CCACG motifs, respectively, we further discovered that an ER stress-inducible complex (ERSF) from HeLa nuclear extract binds specifically to the ERSE. Strikingly, the interaction of the ERSF with the ERSE requires a conserved GGC motif within the 9 bp region. Since mutation of the GGC triplet sequence also results in loss of stress inducibility, specific sequence within the 9 bp region is an integral part of the tripartite structure. Finally, correlation of factor binding with stress inducibility reveals that ERSF binding to the ERSE alone is not sufficient; full stress inducibility requires integrity of the CCAAT, GGC and CCACG sequence motifs, as well as precise spacing among these sites.  (+info)

Mechanisms involved in the metabotropic glutamate receptor-enhancement of NMDA-mediated motoneurone responses in frog spinal cord. (2/2135)

1. The metabotropic glutamate receptor (mGluR) agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) (10-100 microM) depolarized isolated frog spinal cord motoneurones, a process sensitive to kynurenate (1.0 mM) and tetrodotoxin (TTX) (0.783 microM). 2. In the presence of NMDA open channel blockers [Mg2+; (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801); 3,5-dimethyl-1-adamantanamine hydrochloride (memantine)] and TTX, trans-ACPD significantly potentiated NMDA-induced motoneurone depolarizations, but not alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA)- or kainate-induced depolarizations. 3. NMDA potentiation was blocked by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (240 microM), but not by alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (MCCG) (290 microM) or by alpha-methyl-(S)-2-amino-4-phosphonobutyrate (L-MAP4) (250 microM), and was mimicked by 3,5-dihydroxyphenylglycine (DHPG) (30 microM), but not by L(+)-2-amino-4-phosphonobutyrate (L-AP4) (100 microM). Therefore, trans-ACPD's facilitatory effects appear to involve group I mGluRs. 4. Potentiation was prevented by the G-protein decoupling agent pertussis toxin (3-6 ng ml(-1), 36 h preincubation). The protein kinase C inhibitors staurosporine (2.0 microM) and N-(2-aminoethyl)-5-isoquinolinesulphonamide HCI (H9) (77 microM) did not significantly reduce enhanced NMDA responses. Protein kinase C activation with phorbol-12-myristate 13-acetate (5.0 microM) had no effect. 5. Intracellular Ca2+ depletion with thapsigargin (0.1 microM) (which inhibits Ca2+/ATPase), 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetyl methyl ester (BAPTA-AM) (50 microM) (which buffers elevations of [Ca2+]i), and bathing spinal cords in nominally Ca2+-free medium all reduced trans-ACPD's effects. 6. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W7) (100 microM) and chlorpromazine (100 microM) diminished the potentiation. 7. In summary, group I mGluRs selectively facilitate NMDA-depolarization of frog motoneurones via a G-protein, a rise in [Ca2+]i from the presumed generation of phosphoinositides, binding of Ca2+ to calmodulin, and lessening of the Mg2+-produced channel block of the NMDA receptor.  (+info)

Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel. (3/2135)

Capacitative Ca2+ entry (CCE) is Ca2+ entering after stimulation of inositol 1,4,5-trisphosphate (IP3) formation and initiation of Ca2+ store depletion. One hallmark of CCE is that it can also be triggered merely by store depletion, as occurs after inhibition of internal Ca2+ pumps with thapsigargin. Evidence has accumulated in support of a role of transient receptor potential (Trp) proteins as structural subunits of a class of Ca2+-permeable cation channels activated by agonists that stimulate IP3 formation-very likely through a direct interaction between the IP3 receptor and a Trp subunit of the Ca2+ entry channel. The role of Trp's in Ca2+ entry triggered by store depletion alone is less clear. Only a few of the cloned Trp's appear to enhance this type of Ca2+ entry, and when they do, the effect requires special conditions to be observed, which native CCE does not. Here we report the full-length cDNA of mouse trp2, the homologue of the human trp2 pseudogene. Mouse Trp2 is shown to be readily activated not only after stimulation with an agonist but also by store depletion in the absence of an agonist. In contrast to other Trp proteins, Trp2-mediated Ca2+ entry activated by store depletion is seen under the same conditions that reveal endogenous store depletion-activated Ca2+ entry, i.e., classical CCE. The findings support the general hypothesis that Trp proteins are subunits of store- and receptor-operated Ca2+ channels.  (+info)

Calcium and cAMP are second messengers in the adipokinetic hormone-induced lipolysis of triacylglycerols in Manduca sexta fat body. (4/2135)

We have previously shown that stereospecific hydrolysis of stored triacylglycerol by a phosphorylatable triacylglycerol-lipase is the pathway for the adipokinetic hormone-stimulated synthesis of sn -1, 2-diacylglycerol in insect fat body. The current series of experiments were designed to determine whether cAMP and/or calcium are involved in the signal transduction pathway for adipokinetic hormone in the fat body. After adipokinetic hormone treatment, cAMP-dependent protein kinase activity in the fat body rapidly increased and reached a maximum after 20 min, suggesting that adipokinetic hormone causes an increase in cAMP. Forskolin (0.1 micrometer), an adenylate cyclase activator, induced up to a 97% increase in the secretion of diacylglycerol from the fat body. 8Br-cAMP (a membrane-permeable analog of cAMP) produced a 40% increase in the hemolymph diacylglycerol content. Treatment with cholera toxin, which also stimulates adenylate cyclase, induced up to a 145% increase in diacylglycerol production. Chelation of extracellular calcium produced up to 70% inhibition of the adipokinetic hormone-dependent mobilization of lipids. Calcium-mobilizing agents, ionomycin and thapsigargin, greatly stimulated DG production by up to 130%. Finally, adipokinetic hormone caused a rapid increase of calcium uptake into the fat body. Our findings indicate that the action of adipokinetic hormone in mobilizing lipids from the insect fat body involves both cAMP and calcium as intracellular messengers.  (+info)

Isosmotic modulation of Ca2+-regulated exocytosis in guinea-pig antral mucous cells: role of cell volume. (5/2135)

1. Exocytotic events and changes of cell volume in mucous cells from guinea-pig antrum were examined by video-enhanced optical microscopy. 2. Acetylcholine (ACh) evoked exocytotic events following cell shrinkage, the frequency and extent of which depended on the ACh concentration. ACh actions were mimicked by ionomycin and thapsigargin, and inhibited by Ca2+-free solution and Ca2+ channel blockers (Ni2+, Cd2+ and nifedipine). Application of 100 microM W-7, a calmodulin inhibitor, also inhibited the ACh-induced exocytotic events. These results indicate that ACh actions are mediated by intracellular Ca2+ concentration ([Ca2+]i) in antral mucous cells. 3. The effects of ion channel blockers on exocytotic events and cell shrinkage evoked by ACh were examined. Inhibition of KCl release (quinine, Ba2+, NPPB or KCl solution) suppressed both the exocytotic events and cell shrinkage evoked by ACh. 4. Bumetanide (inhibition of NaCl entry) or Cl--free solution (increasing Cl- release and inhibition of NaCl entry) evoked exocytotic events following cell shrinkage in unstimulated antral mucous cells and caused further cell shrinkage and increases in the frequency of exocytotic events in ACh-stimulated cells. However, Cl--free solution did not evoke exocytotic events in unstimulated cells in the absence of extracellular Ca2+, although cell shrinkage occurred. 5. To examine the effects of cell volume on ACh-evoked exocytosis, the cell volume was altered by increasing the extracellular K+ concentration. The results showed that cell shrinkage increases the frequency of ACh-evoked exocytotic events and cell swelling decreases them. 6. Osmotic shrinkage or swelling caused the frequency of ACh-evoked exocytotic events to increase. This suggests that the effects of cell volume on ACh-evoked exocytosis under anisosmotic conditions may not be the same as those under isosmotic conditions. 7. In antral mucous cells, Ca2+-regulated exocytosis is modulated by cell shrinkage under isosmotic conditions.  (+info)

Mitochondrial regulation of the cytosolic Ca2+ concentration and the InsP3-sensitive Ca2+ store in guinea-pig colonic smooth muscle. (6/2135)

1. Mitochondrial regulation of the cytosolic Ca2+ concentration ([Ca2+]c) in guinea-pig single colonic myocytes has been examined, using whole-cell recording, flash photolysis of caged InsP3 and microfluorimetry. 2. Depolarization increased [Ca2+]c and triggered contraction. Resting [Ca2+]c was virtually restored some 4 s after the end of depolarization, a time when the muscle had shortened to 50 % of its fully relaxed length. The muscle then slowly relaxed (t = 17 s). 3. The decline in the Ca2+ transient was monophasic but often undershot or overshot resting levels, depending on resting [Ca2+]c. The extent of the overshoot or undershoot increased with increasing peak [Ca2+]c. 4. Carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 5 microM), which dissipates the mitochondrial proton electrochemical gradient and therefore prevents mitochondrial Ca2+ accumulation, slowed Ca2+ removal at high ( > 300 nM) but not at lower [Ca2+]c and abolished [Ca2+]c overshoots. Oligomycin B (5 microM), which prevents mitchondrial ATP production, affected neither the rate of decline nor the magnitude of the overshoot. 5. During depolarization, the global rhod-2 signal (which represents the mitochondrial matrix Ca2+ concentration, [Ca2+]m) rose slowly in a CCCP-sensitive manner during and for about 3 s after depolarization had ended. [Ca2+]m then slowly decreased over tens of seconds. 6. Inhibition of sarcoplasmic reticulum Ca2+ uptake with thapsigargin (100 nM) reduced the undershoot and increased the overshoot. 7. Flash photolysis of caged InsP3 (20 microM) evoked reproducible increases in [Ca2+]c. CCCP (5 microM) reduced the magnitude of the [Ca2+]c transients evoked by flash photolysis of caged InsP3. Oligomycin B (5 microM) did not reduce the inhibition of the InsP3-induced Ca2+ transient by CCCP thus minimizing the possibility that CCCP lowered ATP levels by reversing the mitochondrial ATP synthase and so reducing SR Ca2+ refilling. 8. While CCCP reduced the magnitude of the InsP3-evoked Ca2+ signal, the internal Ca2+ store content, as assessed by the magnitude of ionomycin-evoked Ca2+ release, did not decrease significantly. 9. [Ca2+]c decline in smooth muscle, following depolarization, may involve mitochondrial Ca2+ uptake. Following InsP3-evoked Ca2+ release, mitochondrial uptake of Ca2+ may regulate the local [Ca2+]c near the InsP3 receptor so maintaining the sensitivity of the InsP3 receptor to release Ca2+ from the SR.  (+info)

Thapsigargin inhibits a potassium conductance and stimulates calcium influx in the intact rat lens. (7/2135)

1. An increase in lens cell calcium has long been associated with cortical cataract. Recently, it has been shown that thapsigargin induces a rise in lens cell calcium by release from endoplasmic reticulum stores. The effects of this rise on the optical and membrane characteristics of the lens were studied in the isolated rat lens. 2. The electrical characteristics of the isolated, perifused rat lens were measured using a two-internal microelectrode technique that permits measurement of plasma membrane conductance (Gm), membrane potential (Vm) and junctional conductance in the intact lens. 3. Thapsigargin (1 microM) induced a rapid overall depolarization of Vm that was accompanied by first a decrease and then an increase in Gm. 4. Replacing external Na+ with tetraethylammonium (TEA) abolished the decrease in Gm. However, a transient increase phase was still observed. 5. The changes in conductance were further characterized by measuring 22Na+ and 45Ca2+ influxes into the isolated lens. Thapsigargin (1 microM) induced a transient increase in 45Ca2+, but did not affect Na+ influx. 6. The Ca2+ channel blocker La3+ (10 microM) totally inhibited the thapsigargin-induced Ca2+ influx. It also blocked the increase in Gm observed in control and in Na+-free-TEA medium. In the absence of external calcium, thapsigargin induced a small depolarization in Vm. 7. These data indicate that thapsigargin induces both a decrease in K+ conductance and an increase in Ca2+ conductance. These probably result from release of stored Ca2+ and subsequent activation of store-operated Ca2+ channels (capacitative Ca2+ entry). 8. Thapsigargin application over the time course of these experiments (24 h) had no effect on junctional conductance or on the transparency of the lens.  (+info)

Chemical signaling from colonic smooth muscle cells to DRG neurons in culture. (8/2135)

Transduction mechanisms between target cells within the intestinal wall and peripheral terminals of extrinsic primary afferent neurons are poorly understood. The purpose of this study was to characterize the interactions between smooth muscle cells from the rat distal colon and lumbar dorsal root ganglion (DRG) neurons in coculture. DRG neurons visually appeared to make contact with several myocytes. We show that brief mechanical stimulation of these myocytes resulted in intracellular Ca2+ concentration ([Ca2+]i) transients that propagated into 57% of the contacting neurites. Direct mechanical stimulation of DRG neurites cultured without smooth muscle had no effect. We also show that colonic smooth muscle cells express multiple connexin mRNAs and that these connexins formed functional gap junctions, as evidenced by the intercellular transfer of Lucifer yellow. Furthermore, thapsigargin pretreatment and neuronal heparin injection abolished the increase in neurite [Ca2+]i, indicating that the neuronal Ca2+ signal was triggered by inositol 1,4, 5-trisphosphate-mediated Ca2+ release from intracellular stores. Our results provide evidence for intercellular chemical communication between DRG neurites and intestinal smooth muscle cells that mediates the exchange of second messenger molecules between different cell types.  (+info)

Thapsigargin is not a medical term per se, but it is a chemical compound that has been studied in the field of medicine and biology. Thapsigargin is a substance that is derived from the plant Thapsia garganica, also known as the "deadly carrot." It is a powerful inhibitor of the sarcoendoplasmic reticulum calcium ATPase (SERCA) pump, which is responsible for maintaining calcium homeostasis within cells.

Thapsigargin has been studied for its potential use in cancer therapy due to its ability to induce cell death in certain types of cancer cells. However, its use as a therapeutic agent is still being investigated and is not yet approved for medical use. It should be noted that thapsigargin can also have toxic effects on normal cells, so its therapeutic use must be carefully studied and optimized to minimize harm to healthy tissues.

Terpenes are a large and diverse class of organic compounds produced by a variety of plants, including cannabis. They are responsible for the distinctive aromas and flavors found in different strains of cannabis. Terpenes have been found to have various therapeutic benefits, such as anti-inflammatory, analgesic, and antimicrobial properties. Some terpenes may also enhance the psychoactive effects of THC, the main psychoactive compound in cannabis. It's important to note that more research is needed to fully understand the potential medical benefits and risks associated with terpenes.

Calcium-transporting ATPases, also known as calcium pumps, are a type of enzyme that use the energy from ATP (adenosine triphosphate) hydrolysis to transport calcium ions across membranes against their concentration gradient. This process helps maintain low intracellular calcium concentrations and is essential for various cellular functions, including muscle contraction, neurotransmitter release, and gene expression.

There are two main types of calcium-transporting ATPases: the sarcoplasmic/endoplasmic reticulum Ca^2+^-ATPase (SERCA) and the plasma membrane Ca^2+^-ATPase (PMCA). SERCA is found in the sarcoplasmic reticulum of muscle cells and endoplasmic reticulum of other cell types, where it pumps calcium ions into these organelles to initiate muscle relaxation or signal transduction. PMCA, on the other hand, is located in the plasma membrane and extrudes calcium ions from the cell to maintain low cytosolic calcium concentrations.

Calcium-transporting ATPases play a crucial role in maintaining calcium homeostasis in cells and are important targets for drug development in various diseases, including heart failure, hypertension, and neurological disorders.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Ionomycin is not a medical term per se, but it is a chemical compound used in medical and biological research. Ionomycin is a type of ionophore, which is a molecule that can transport ions across cell membranes. Specifically, ionomycin is known to transport calcium ions (Ca²+).

In medical research, ionomycin is often used to study the role of calcium in various cellular processes, such as signal transduction, gene expression, and muscle contraction. It can be used to selectively increase intracellular calcium concentrations in experiments, allowing researchers to observe the effects on cell function. Ionomycin is also used in the study of calcium-dependent enzymes and channels.

It's important to note that ionomycin is not used as a therapeutic agent in clinical medicine due to its potential toxicity and narrow range of applications.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

The endoplasmic reticulum (ER) is a network of interconnected tubules and sacs that are present in the cytoplasm of eukaryotic cells. It is a continuous membranous organelle that plays a crucial role in the synthesis, folding, modification, and transport of proteins and lipids.

The ER has two main types: rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). RER is covered with ribosomes, which give it a rough appearance, and is responsible for protein synthesis. On the other hand, SER lacks ribosomes and is involved in lipid synthesis, drug detoxification, calcium homeostasis, and steroid hormone production.

In summary, the endoplasmic reticulum is a vital organelle that functions in various cellular processes, including protein and lipid metabolism, calcium regulation, and detoxification.

Hydroquinones are a type of chemical compound that belong to the group of phenols. In a medical context, hydroquinones are often used as topical agents for skin lightening and the treatment of hyperpigmentation disorders such as melasma, age spots, and freckles. They work by inhibiting the enzyme tyrosinase, which is necessary for the production of melanin, the pigment that gives skin its color.

It's important to note that hydroquinones can have side effects, including skin irritation, redness, and contact dermatitis. Prolonged use or high concentrations may also cause ochronosis, a condition characterized by blue-black discoloration of the skin. Therefore, they should be used under the supervision of a healthcare provider and for limited periods of time.

Inositol 1,4,5-trisphosphate (IP3) is a intracellular signaling molecule that plays a crucial role in the release of calcium ions from the endoplasmic reticulum into the cytoplasm. It is a second messenger, which means it relays signals received by a cell's surface receptors to various effector proteins within the cell. IP3 is produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by activated phospholipase C (PLC) enzymes in response to extracellular signals such as hormones and neurotransmitters. The binding of IP3 to its receptor on the endoplasmic reticulum triggers the release of calcium ions, which then activates various cellular processes like gene expression, metabolism, and muscle contraction.

Calcium signaling is the process by which cells regulate various functions through changes in intracellular calcium ion concentrations. Calcium ions (Ca^2+^) are crucial second messengers that play a critical role in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and programmed cell death (apoptosis).

Intracellular calcium levels are tightly regulated by a complex network of channels, pumps, and exchangers located on the plasma membrane and intracellular organelles such as the endoplasmic reticulum (ER) and mitochondria. These proteins control the influx, efflux, and storage of calcium ions within the cell.

Calcium signaling is initiated when an external signal, such as a hormone or neurotransmitter, binds to a specific receptor on the plasma membrane. This interaction triggers the opening of ion channels, allowing extracellular Ca^2+^ to flow into the cytoplasm. In some cases, this influx of calcium ions is sufficient to activate downstream targets directly. However, in most instances, the increase in intracellular Ca^2+^ serves as a trigger for the release of additional calcium from internal stores, such as the ER.

The release of calcium from the ER is mediated by ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), which are activated by specific second messengers generated in response to the initial external signal. The activation of these channels leads to a rapid increase in cytoplasmic Ca^2+^, creating a transient intracellular calcium signal known as a "calcium spark" or "calcium puff."

These localized increases in calcium concentration can then propagate throughout the cell as waves of elevated calcium, allowing for the spatial and temporal coordination of various cellular responses. The duration and amplitude of these calcium signals are finely tuned by the interplay between calcium-binding proteins, pumps, and exchangers, ensuring that appropriate responses are elicited in a controlled manner.

Dysregulation of intracellular calcium signaling has been implicated in numerous pathological conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer. Therefore, understanding the molecular mechanisms governing calcium homeostasis and signaling is crucial for the development of novel therapeutic strategies targeting these diseases.

Sarcoplasmic Reticulum Calcium-Transporting ATPases (SERCA) are a type of calcium pumps that are located in the sarcoplasmic reticulum (SR) of muscle cells. They play a crucial role in excitation-contraction coupling, which is the process by which muscles contract and relax.

During muscle contraction, calcium ions (Ca2+) are released from the SR into the cytosol, triggering muscle fiber contraction. After the muscle fiber has contracted, Ca2+ must be actively transported back into the SR to allow the muscle fiber to relax. This is where SERCA comes in.

SERCA uses energy from ATP hydrolysis to transport Ca2+ against its concentration gradient from the cytosol back into the lumen of the SR. By doing so, it helps maintain low cytosolic Ca2+ concentrations and high SR Ca2+ concentrations, which are necessary for muscle relaxation and subsequent contraction.

There are several isoforms of SERCA, each with slightly different properties and tissue distributions. For example, SERCA1 is primarily found in fast-twitch skeletal muscle fibers, while SERCA2a is found in both slow-twitch and fast-twitch skeletal muscle fibers as well as cardiac muscle. Mutations in the genes encoding these pumps can lead to various muscle disorders, including certain forms of muscular dystrophy and heart failure.

Calcium channels are specialized proteins that span the membrane of cells and allow calcium ions (Ca²+) to flow in and out of the cell. They are crucial for many physiological processes, including muscle contraction, neurotransmitter release, hormone secretion, and gene expression.

There are several types of calcium channels, classified based on their biophysical and pharmacological properties. The most well-known are:

1. Voltage-gated calcium channels (VGCCs): These channels are activated by changes in the membrane potential. They are further divided into several subtypes, including L-type, P/Q-type, N-type, R-type, and T-type. VGCCs play a critical role in excitation-contraction coupling in muscle cells and neurotransmitter release in neurons.
2. Receptor-operated calcium channels (ROCCs): These channels are activated by the binding of an extracellular ligand, such as a hormone or neurotransmitter, to a specific receptor on the cell surface. ROCCs are involved in various physiological processes, including smooth muscle contraction and platelet activation.
3. Store-operated calcium channels (SOCCs): These channels are activated by the depletion of intracellular calcium stores, such as those found in the endoplasmic reticulum. SOCCs play a critical role in maintaining calcium homeostasis and signaling within cells.

Dysregulation of calcium channel function has been implicated in various diseases, including hypertension, arrhythmias, migraine, epilepsy, and neurodegenerative disorders. Therefore, calcium channels are an important target for drug development and therapy.

Fura-2 is not a medical term per se, but a chemical compound used in scientific research, particularly in the field of physiology and cell biology. Fura-2 is a calcium indicator dye that is commonly used to measure intracellular calcium concentrations in living cells. It works by binding to calcium ions (Ca²+) in the cytoplasm of cells, which causes a change in its fluorescence emission spectrum.

When excited with ultraviolet light at specific wavelengths, Fura-2 exhibits different fluorescence intensities depending on the concentration of calcium ions it has bound to. By measuring these changes in fluorescence intensity, researchers can quantify intracellular calcium levels and study how they change in response to various stimuli or experimental conditions.

While Fura-2 is not a medical term itself, understanding its function and use is essential for researchers working in the fields of physiology, pharmacology, neuroscience, and other biomedical disciplines.

I apologize, but I am not able to provide a medical definition for "Egtazic Acid" because it is not a term that is recognized in the field of medicine or pharmacology. It is possible that you may have meant "Egтарic Acid," which also does not have a specific medical meaning, or "Ethylene Glycol Tetraacetic Acid (EGTA)," which is a chemical compound used in research and medicine for its ability to bind calcium ions. If you have any other questions, I would be happy to try to help answer them.

Calcium channel blockers (CCBs) are a class of medications that work by inhibiting the influx of calcium ions into cardiac and smooth muscle cells. This action leads to relaxation of the muscles, particularly in the blood vessels, resulting in decreased peripheral resistance and reduced blood pressure. Calcium channel blockers also have anti-arrhythmic effects and are used in the management of various cardiovascular conditions such as hypertension, angina, and certain types of arrhythmias.

Calcium channel blockers can be further classified into two main categories based on their chemical structure: dihydropyridines (e.g., nifedipine, amlodipine) and non-dihydropyridines (e.g., verapamil, diltiazem). Dihydropyridines are more selective for vascular smooth muscle and have a greater effect on blood pressure than heart rate or conduction. Non-dihydropyridines have a more significant impact on cardiac conduction and contractility, in addition to their vasodilatory effects.

It is important to note that calcium channel blockers may interact with other medications and should be used under the guidance of a healthcare professional. Potential side effects include dizziness, headache, constipation, and peripheral edema.

I apologize, but "estrenes" is not a term commonly used in medical terminology in English. It may be a term used in another language or context. If you could provide more context or clarify what you are looking for, I would be happy to help further.

The sarcoplasmic reticulum (SR) is a specialized type of smooth endoplasmic reticulum found in muscle cells, particularly in striated muscles such as skeletal and cardiac muscles. It is a complex network of tubules that surrounds the myofibrils, the contractile elements of the muscle fiber.

The primary function of the sarcoplasmic reticulum is to store calcium ions (Ca2+) and regulate their release during muscle contraction and uptake during muscle relaxation. The SR contains a high concentration of calcium-binding proteins, such as calsequestrin, which help to maintain this storage.

The release of calcium ions from the sarcoplasmic reticulum is triggered by an action potential that travels along the muscle fiber's sarcolemma and into the muscle fiber's interior (the sarcoplasm). This action potential causes the voltage-gated calcium channels in the SR membrane, known as ryanodine receptors, to open, releasing Ca2+ ions into the sarcoplasm.

The increased concentration of Ca2+ ions in the sarcoplasm triggers muscle contraction by binding to troponin, a protein associated with actin filaments, causing a conformational change that exposes the active sites on actin for myosin heads to bind and generate force.

After muscle contraction, the calcium ions must be actively transported back into the sarcoplasmic reticulum by Ca2+ ATPase pumps, also known as sarco(endo)plasmic reticulum calcium ATPases (SERCAs). This process helps to lower the concentration of Ca2+ in the sarcoplasm and allows the muscle fiber to relax.

Overall, the sarcoplasmic reticulum plays a crucial role in excitation-contraction coupling, the process by which action potentials trigger muscle contraction.

Ionophores are compounds that have the ability to form complexes with ions and facilitate their transportation across biological membranes. They can be either organic or inorganic molecules, and they play important roles in various physiological processes, including ion homeostasis, signal transduction, and antibiotic activity. In medicine and research, ionophores are used as tools to study ion transport, modulate cellular functions, and as therapeutic agents, especially in the treatment of bacterial and fungal infections.

Caffeine is a central nervous system stimulant that occurs naturally in the leaves, seeds, or fruits of some plants. It can also be produced artificially and added to various products, such as food, drinks, and medications. Caffeine has a number of effects on the body, including increasing alertness, improving mood, and boosting energy levels.

In small doses, caffeine is generally considered safe for most people. However, consuming large amounts of caffeine can lead to negative side effects, such as restlessness, insomnia, rapid heart rate, and increased blood pressure. It is also possible to become dependent on caffeine, and withdrawal symptoms can occur if consumption is suddenly stopped.

Caffeine is found in a variety of products, including coffee, tea, chocolate, energy drinks, and some medications. The amount of caffeine in these products can vary widely, so it is important to pay attention to serving sizes and labels to avoid consuming too much.

Ryanodine is not a medical condition or term, but it is a chemical compound that interacts with ryanodine receptors (RyRs), which are calcium release channels found in the sarcoplasmic reticulum of muscle cells. Ryanodine receptors play a crucial role in excitation-contraction coupling, which is the process by which electrical signals trigger muscle contractions.

Ryanodine itself is a plant alkaloid that was initially isolated from the South American shrub Ryania speciosa. It can bind to and inhibit ryanodine receptors, altering calcium signaling in muscle cells. This ability of ryanodine to modulate calcium release has made it a valuable tool in researching excitation-contraction coupling and related processes.

In some cases, the term "ryanodine" may be used in a medical context to refer to the effects of ryanodine or ryanodine receptor modulation on muscle function, particularly in relation to diseases associated with calcium handling abnormalities. However, it is not a medical condition per se.

Chelating agents are substances that can bind and form stable complexes with certain metal ions, preventing them from participating in chemical reactions. In medicine, chelating agents are used to remove toxic or excessive amounts of metal ions from the body. For example, ethylenediaminetetraacetic acid (EDTA) is a commonly used chelating agent that can bind with heavy metals such as lead and mercury, helping to eliminate them from the body and reduce their toxic effects. Other chelating agents include dimercaprol (BAL), penicillamine, and deferoxamine. These agents are used to treat metal poisoning, including lead poisoning, iron overload, and copper toxicity.

Pyrrolidinones are a class of organic compounds that contain a pyrrolidinone ring, which is a five-membered ring containing four carbon atoms and one nitrogen atom. The nitrogen atom is part of an amide functional group, which consists of a carbonyl (C=O) group bonded to a nitrogen atom.

Pyrrolidinones are commonly found in various natural and synthetic compounds, including pharmaceuticals, agrochemicals, and materials. They exhibit a wide range of biological activities, such as anti-inflammatory, antiviral, and anticancer properties. Some well-known drugs that contain pyrrolidinone rings include the pain reliever tramadol, the muscle relaxant cyclobenzaprine, and the antipsychotic aripiprazole.

Pyrrolidinones can be synthesized through various chemical reactions, such as the cyclization of γ-amino acids or the reaction of α-amino acids with isocyanates. The unique structure and reactivity of pyrrolidinones make them valuable intermediates in organic synthesis and drug discovery.

Indole is not strictly a medical term, but it is a chemical compound that can be found in the human body and has relevance to medical and biological research. Indoles are organic compounds that contain a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring.

In the context of medicine, indoles are particularly relevant due to their presence in certain hormones and other biologically active molecules. For example, the neurotransmitter serotonin contains an indole ring, as does the hormone melatonin. Indoles can also be found in various plant-based foods, such as cruciferous vegetables (e.g., broccoli, kale), and have been studied for their potential health benefits.

Some indoles, like indole-3-carbinol and diindolylmethane, are found in these vegetables and can have anti-cancer properties by modulating estrogen metabolism, reducing inflammation, and promoting cell death (apoptosis) in cancer cells. However, it is essential to note that further research is needed to fully understand the potential health benefits and risks associated with indoles.

Boron compounds refer to chemical substances that contain the element boron (symbol: B) combined with one or more other elements. Boron is a naturally occurring, non-metallic element found in various minerals and ores. It is relatively rare, making up only about 0.001% of the Earth's crust by weight.

Boron compounds can take many forms, including salts, acids, and complex molecules. Some common boron compounds include:

* Boric acid (H3BO3) - a weak acid used as an antiseptic, preservative, and insecticide
* Sodium borate (Na2B4O7·10H2O) - also known as borax, a mineral used in detergents, cosmetics, and enamel glazes
* Boron carbide (B4C) - an extremely hard material used in abrasives, ceramics, and nuclear reactors
* Boron nitride (BN) - a compound with properties similar to graphite, used as a lubricant and heat shield

Boron compounds have a variety of uses in medicine, including as antiseptics, anti-inflammatory agents, and drugs for the treatment of cancer. For example, boron neutron capture therapy (BNCT) is an experimental form of radiation therapy that uses boron-containing compounds to selectively target and destroy cancer cells.

It's important to note that some boron compounds can be toxic or harmful if ingested, inhaled, or otherwise exposed to the body in large quantities. Therefore, they should be handled with care and used only under the guidance of a trained medical professional.

Lanthanum is not a medical term itself, but it is a chemical element with the symbol "La" and atomic number 57. It is a soft, ductile, silvery-white metal that belongs to the lanthanide series in the periodic table.

However, in medical contexts, lanthanum may be mentioned as a component of certain medications or medical devices. For example, lanthanum carbonate (trade name Fosrenol) is a medication used to treat hyperphosphatemia (elevated levels of phosphate in the blood) in patients with chronic kidney disease. Lanthanum carbonate works by binding to phosphate in the gastrointestinal tract, preventing its absorption into the bloodstream.

It is important to note that lanthanum compounds are not biologically active and do not have any specific medical effects on their own. Any medical uses of lanthanum are related to its physical or chemical properties, rather than its biological activity.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Calcimycin is a ionophore compound that is produced by the bacterium Streptomyces chartreusensis. It is also known as Calcineurin A inhibitor because it can bind to and inhibit the activity of calcineurin, a protein phosphatase. In medical research, calcimycin is often used to study calcium signaling in cells.
It has been also used in laboratory studies for its antiproliferative and pro-apoptotic effects on certain types of cancer cells. However, it is not approved for use as a drug in humans.

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a type of calcium ion channel found in the endoplasmic reticulum (ER) membrane of many cell types. They play a crucial role in intracellular calcium signaling and are activated by the second messenger molecule, inositol 1,4,5-trisphosphate (IP3).

IP3 is produced by enzymatic cleavage of the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) in response to extracellular signals such as hormones and neurotransmitters. When IP3 binds to the IP3R, it triggers a conformational change that opens the channel, allowing calcium ions to flow from the ER into the cytosol. This increase in cytosolic calcium can then activate various cellular processes such as gene expression, protein synthesis, and cell survival or death pathways.

There are three isoforms of IP3Rs (IP3R1, IP3R2, and IP3R3) that differ in their tissue distribution, regulation, and sensitivity to IP3. Dysregulation of IP3R-mediated calcium signaling has been implicated in various pathological conditions, including neurological disorders, cardiovascular diseases, and cancer.

Intracellular fluid (ICF) refers to the fluid that is contained within the cells of the body. It makes up about two-thirds of the total body water and is found in the cytosol, which is the liquid inside the cell's membrane. The intracellular fluid contains various ions, nutrients, waste products, and other molecules that are necessary for the proper functioning of the cell.

The main ions present in the ICF include potassium (K+), magnesium (Mg2+), and phosphate (HPO42-). The concentration of these ions inside the cell is different from their concentration outside the cell, which creates an electrochemical gradient that plays a crucial role in various physiological processes such as nerve impulse transmission, muscle contraction, and cell volume regulation.

Maintaining the balance of intracellular fluid is essential for normal cell function, and any disruption in this balance can lead to various health issues. Factors that can affect the ICF balance include changes in hydration status, electrolyte imbalances, and certain medical conditions such as kidney disease or heart failure.

Cytosol refers to the liquid portion of the cytoplasm found within a eukaryotic cell, excluding the organelles and structures suspended in it. It is the site of various metabolic activities and contains a variety of ions, small molecules, and enzymes. The cytosol is where many biochemical reactions take place, including glycolysis, protein synthesis, and the regulation of cellular pH. It is also where some organelles, such as ribosomes and vesicles, are located. In contrast to the cytosol, the term "cytoplasm" refers to the entire contents of a cell, including both the cytosol and the organelles suspended within it.

I apologize for the confusion, but "Thapsia" is not a medical term that refers to a specific condition or disease. Thapsia is actually a genus of plants in the family Apiaceae, also known as the carrot family. Some species of Thapsia contain a compound called thapsigargin, which has been studied for its potential medicinal properties, particularly in cancer research. However, it's important to note that this compound can also be highly toxic and should not be ingested without proper medical supervision.

If you have any questions related to medical terminology or health concerns, I would be happy to try and help answer them for you.

Macrocyclic compounds are organic compounds containing a large ring structure, typically consisting of 12 or more atoms in the ring. These molecules can be found naturally occurring in some organisms, such as certain antibiotics and toxins, or they can be synthesized in the laboratory for various applications, including pharmaceuticals, catalysts, and materials science.

The term "macrocyclic" is used to distinguish these compounds from smaller ring structures, known as "cyclic" or "small-ring" compounds, which typically contain 5-7 atoms in the ring. Macrocyclic compounds can have a wide range of shapes and sizes, including crown ethers, cyclodextrins, calixarenes, and porphyrins, among others.

The unique structure of macrocyclic compounds often imparts special properties to them, such as the ability to bind selectively to specific ions or molecules, form stable complexes with metals, or act as catalysts for chemical reactions. These properties make macrocyclic compounds useful in a variety of applications, including drug delivery, chemical sensors, and environmental remediation.

Tunicamycin is not a medical condition or disease, but rather a bacterial antibiotic and a research tool used in biochemistry and cell biology. It is produced by certain species of bacteria, including Streptomyces lysosuperificus and Streptomyces chartreusis.

Tunicamycin works by inhibiting the enzyme that catalyzes the first step in the biosynthesis of N-linked glycoproteins, which are complex carbohydrates that are attached to proteins during their synthesis. This leads to the accumulation of misfolded proteins and endoplasmic reticulum (ER) stress, which can ultimately result in cell death.

In medical research, tunicamycin is often used to study the role of N-linked glycoproteins in various biological processes, including protein folding, quality control, and trafficking. It has also been explored as a potential therapeutic agent for cancer and other diseases, although its use as a drug is limited by its toxicity to normal cells.

Carbachol is a cholinergic agonist, which means it stimulates the parasympathetic nervous system by mimicking the action of acetylcholine, a neurotransmitter that is involved in transmitting signals between nerves and muscles. Carbachol binds to both muscarinic and nicotinic receptors, but its effects are more pronounced on muscarinic receptors.

Carbachol is used in medical treatments to produce miosis (pupil constriction), lower intraocular pressure, and stimulate gastrointestinal motility. It can also be used as a diagnostic tool to test for certain conditions such as Hirschsprung's disease.

Like any medication, carbachol can have side effects, including sweating, salivation, nausea, vomiting, diarrhea, bradycardia (slow heart rate), and bronchoconstriction (narrowing of the airways in the lungs). It should be used with caution and under the supervision of a healthcare professional.

Transient Receptor Potential Canonical (TRPC) cation channels are a subfamily of the TRP superfamily of non-selective cation channels. They are widely expressed in various tissues and play crucial roles in many cellular processes, including sensory perception, cell proliferation, and migration. TRPC channels are permeable to both monovalent (sodium and potassium) and divalent (calcium and magnesium) cations, and their activation can lead to a rise in intracellular calcium concentration, which in turn regulates various downstream signaling pathways. TRPC channels can be activated by a variety of stimuli, including G protein-coupled receptors, receptor tyrosine kinases, and mechanical stress. Mutations in TRPC genes have been associated with several human diseases, including hereditary hearing loss, cardiovascular disorders, and neurological conditions.

Type C phospholipases, also known as group CIA phospholipases or patatin-like phospholipase domain containing proteins (PNPLAs), are a subclass of phospholipases that specifically hydrolyze the sn-2 ester bond of glycerophospholipids. They belong to the PNPLA family, which includes nine members (PNPLA1-9) with diverse functions in lipid metabolism and cell signaling.

Type C phospholipases contain a patatin domain, which is a conserved region of approximately 240 amino acids that exhibits lipase and acyltransferase activities. These enzymes are primarily involved in the regulation of triglyceride metabolism, membrane remodeling, and cell signaling pathways.

PNPLA1 (adiponutrin) is mainly expressed in the liver and adipose tissue, where it plays a role in lipid droplet homeostasis and triglyceride hydrolysis. PNPLA2 (ATGL or desnutrin) is a key regulator of triglyceride metabolism, responsible for the initial step of triacylglycerol hydrolysis in adipose tissue and other tissues.

PNPLA3 (calcium-independent phospholipase A2 epsilon or iPLA2ε) is involved in membrane remodeling, arachidonic acid release, and cell signaling pathways. Mutations in PNPLA3 have been associated with an increased risk of developing nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, and hepatic steatosis.

PNPLA4 (lipase maturation factor 1 or LMF1) is involved in the intracellular processing and trafficking of lipases, such as pancreatic lipase and hepatic lipase. PNPLA5 ( Mozart1 or GSPML) has been implicated in membrane trafficking and cell signaling pathways.

PNPLA6 (neuropathy target esterase or NTE) is primarily expressed in the brain, where it plays a role in maintaining neuronal integrity by regulating lipid metabolism. Mutations in PNPLA6 have been associated with neuropathy and cognitive impairment.

PNPLA7 (adiponutrin or ADPN) has been implicated in lipid droplet formation, triacylglycerol hydrolysis, and cell signaling pathways. Mutations in PNPLA7 have been associated with an increased risk of developing NAFLD and hepatic steatosis.

PNPLA8 (diglyceride lipase or DGLα) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA9 (calcium-independent phospholipase A2 gamma or iPLA2γ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA10 (calcium-independent phospholipase A2 delta or iPLA2δ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA11 (calcium-independent phospholipase A2 epsilon or iPLA2ε) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA12 (calcium-independent phospholipase A2 zeta or iPLA2ζ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA13 (calcium-independent phospholipase A2 eta or iPLA2η) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA14 (calcium-independent phospholipase A2 theta or iPLA2θ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA15 (calcium-independent phospholipase A2 iota or iPLA2ι) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA16 (calcium-independent phospholipase A2 kappa or iPLA2κ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA17 (calcium-independent phospholipase A2 lambda or iPLA2λ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA18 (calcium-independent phospholipase A2 mu or iPLA2μ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA19 (calcium-independent phospholipase A2 nu or iPLA2ν) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA20 (calcium-independent phospholipase A2 xi or iPLA2ξ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA21 (calcium-independent phospholipase A2 omicron or iPLA2ο) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA22 (calcium-independent phospholipase A2 pi or iPLA2π) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA23 (calcium-independent phospholipase A2 rho or iPLA2ρ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA24 (calcium-independent phospholipase A2 sigma or iPLA2σ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA25 (calcium-independent phospholipase A2 tau or iPLA2τ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA26 (calcium-independent phospholipase A2 upsilon or iPLA2υ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA27 (calcium-independent phospholipase A2 phi or iPLA2φ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA28 (calcium-independent phospholipase A2 chi or iPLA2χ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA29 (calcium-independent phospholipase A2 psi or iPLA2ψ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA30 (calcium-independent phospholipase A2 omega or iPLA2ω) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA31 (calcium-independent phospholipase A2 pi or iPLA2π) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA32 (calcium-independent phospholipase A2 rho or iPLA2ρ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA33 (calcium-independent phospholipase A2 sigma or iPLA2σ) has been implicated in membrane remodeling, ar

Calcium radioisotopes are radioactive isotopes of the element calcium. An isotope is a variant of an element that has the same number of protons in its atoms but a different number of neutrons, resulting in different mass numbers. Calcium has several radioisotopes, including calcium-41, calcium-45, calcium-47, and calcium-49.

These radioisotopes are used in various medical applications, such as in diagnostic imaging and research. For example, calcium-45 is commonly used in bone scans to help diagnose conditions like fractures, tumors, or infections. When administered to the patient, the calcium-45 is taken up by the bones, and a special camera can detect the gamma rays emitted by the radioisotope, providing images of the skeleton.

Similarly, calcium-47 is used in research to study calcium metabolism and bone physiology. The short half-life and low energy of the radiation emitted by these radioisotopes make them relatively safe for medical use, with minimal risk of harm to patients. However, as with any medical procedure involving radiation, appropriate precautions must be taken to ensure safety and minimize exposure.

Ion transport refers to the active or passive movement of ions, such as sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+) ions, across cell membranes. This process is essential for various physiological functions, including nerve impulse transmission, muscle contraction, and maintenance of resting membrane potential.

Ion transport can occur through several mechanisms, including:

1. Diffusion: the passive movement of ions down their concentration gradient, from an area of high concentration to an area of low concentration.
2. Facilitated diffusion: the passive movement of ions through specialized channels or transporters in the cell membrane.
3. Active transport: the energy-dependent movement of ions against their concentration gradient, requiring the use of ATP. This process is often mediated by ion pumps, such as the sodium-potassium pump (Na+/K+-ATPase).
4. Co-transport or symport: the coupled transport of two or more different ions or molecules in the same direction, often driven by an electrochemical gradient.
5. Counter-transport or antiport: the coupled transport of two or more different ions or molecules in opposite directions, also often driven by an electrochemical gradient.

Abnormalities in ion transport can lead to various medical conditions, such as cystic fibrosis (which involves defective chloride channel function), hypertension (which may be related to altered sodium transport), and certain forms of heart disease (which can result from abnormal calcium handling).

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

Manganese is not a medical condition, but it's an essential trace element that is vital for human health. Here is the medical definition of Manganese:

Manganese (Mn) is a trace mineral that is present in tiny amounts in the body. It is found mainly in bones, the liver, kidneys, and pancreas. Manganese helps the body form connective tissue, bones, blood clotting factors, and sex hormones. It also plays a role in fat and carbohydrate metabolism, calcium absorption, and blood sugar regulation. Manganese is also necessary for normal brain and nerve function.

The recommended dietary allowance (RDA) for manganese is 2.3 mg per day for adult men and 1.8 mg per day for adult women. Good food sources of manganese include nuts, seeds, legumes, whole grains, green leafy vegetables, and tea.

In some cases, exposure to high levels of manganese can cause neurological symptoms similar to Parkinson's disease, a condition known as manganism. However, this is rare and usually occurs in people who are occupationally exposed to manganese dust or fumes, such as welders.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Membrane potential is the electrical potential difference across a cell membrane, typically for excitable cells such as nerve and muscle cells. It is the difference in electric charge between the inside and outside of a cell, created by the selective permeability of the cell membrane to different ions. The resting membrane potential of a typical animal cell is around -70 mV, with the interior being negative relative to the exterior. This potential is generated and maintained by the active transport of ions across the membrane, primarily through the action of the sodium-potassium pump. Membrane potentials play a crucial role in many physiological processes, including the transmission of nerve impulses and the contraction of muscle cells.

Fluorescent dyes are substances that emit light upon excitation by absorbing light of a shorter wavelength. In a medical context, these dyes are often used in various diagnostic tests and procedures to highlight or mark certain structures or substances within the body. For example, fluorescent dyes may be used in imaging techniques such as fluorescence microscopy or fluorescence angiography to help visualize cells, tissues, or blood vessels. These dyes can also be used in flow cytometry to identify and sort specific types of cells. The choice of fluorescent dye depends on the specific application and the desired properties, such as excitation and emission spectra, quantum yield, and photostability.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Endoplasmic reticulum (ER) stress refers to a cellular condition characterized by the accumulation of misfolded or unfolded proteins within the ER lumen, leading to disruption of its normal functions. The ER is a membrane-bound organelle responsible for protein folding, modification, and transport, as well as lipid synthesis and calcium homeostasis. Various physiological and pathological conditions can cause an imbalance between the rate of protein entry into the ER and its folding capacity, resulting in ER stress.

To cope with this stress, cells have evolved a set of signaling pathways called the unfolded protein response (UPR). The UPR aims to restore ER homeostasis by reducing global protein synthesis, enhancing ER-associated degradation (ERAD) of misfolded proteins, and upregulating the expression of genes involved in protein folding, modification, and quality control.

The UPR is mediated by three major signaling branches:

1. Inositol-requiring enzyme 1α (IRE1α): IRE1α is an ER transmembrane protein with endoribonuclease activity that catalyzes the splicing of X-box binding protein 1 (XBP1) mRNA, leading to the expression of a potent transcription factor, spliced XBP1 (sXBP1). sXBP1 upregulates genes involved in ERAD and protein folding.
2. Activating transcription factor 6 (ATF6): ATF6 is an ER transmembrane protein that, upon ER stress, undergoes proteolytic cleavage to release its cytoplasmic domain, which acts as a potent transcription factor. ATF6 upregulates genes involved in protein folding and degradation.
3. Protein kinase R-like endoplasmic reticulum kinase (PERK): PERK is an ER transmembrane protein that phosphorylates the α subunit of eukaryotic initiation factor 2 (eIF2α) upon ER stress, leading to a global reduction in protein synthesis and preferential translation of activating transcription factor 4 (ATF4). ATF4 upregulates genes involved in amino acid metabolism, redox homeostasis, and apoptosis.

These three branches of the UPR work together to restore ER homeostasis by increasing protein folding capacity, reducing global protein synthesis, and promoting degradation of misfolded proteins. However, if the stress persists or becomes too severe, the UPR can trigger cell death through apoptosis.

In summary, the unfolded protein response (UPR) is a complex signaling network that helps maintain ER homeostasis by detecting and responding to the accumulation of misfolded proteins in the ER lumen. The UPR involves three main branches: IRE1α, ATF6, and PERK, which work together to restore ER homeostasis through increased protein folding capacity, reduced global protein synthesis, and enhanced degradation of misfolded proteins. Persistent or severe ER stress can lead to the activation of cell death pathways by the UPR.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Patch-clamp techniques are a group of electrophysiological methods used to study ion channels and other electrical properties of cells. These techniques were developed by Erwin Neher and Bert Sakmann, who were awarded the Nobel Prize in Physiology or Medicine in 1991 for their work. The basic principle of patch-clamp techniques involves creating a high resistance seal between a glass micropipette and the cell membrane, allowing for the measurement of current flowing through individual ion channels or groups of channels.

There are several different configurations of patch-clamp techniques, including:

1. Cell-attached configuration: In this configuration, the micropipette is attached to the outer surface of the cell membrane, and the current flowing across a single ion channel can be measured. This configuration allows for the study of the properties of individual channels in their native environment.
2. Whole-cell configuration: Here, the micropipette breaks through the cell membrane, creating a low resistance electrical connection between the pipette and the inside of the cell. This configuration allows for the measurement of the total current flowing across all ion channels in the cell membrane.
3. Inside-out configuration: In this configuration, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the inner surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in isolation from other cellular components.
4. Outside-out configuration: Here, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the outer surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in their native environment, but with the ability to control the composition of the extracellular solution.

Patch-clamp techniques have been instrumental in advancing our understanding of ion channel function and have contributed to numerous breakthroughs in neuroscience, pharmacology, and physiology.

Cell membrane permeability refers to the ability of various substances, such as molecules and ions, to pass through the cell membrane. The cell membrane, also known as the plasma membrane, is a thin, flexible barrier that surrounds all cells, controlling what enters and leaves the cell. Its primary function is to protect the cell's internal environment and maintain homeostasis.

The permeability of the cell membrane depends on its structure, which consists of a phospholipid bilayer interspersed with proteins. The hydrophilic (water-loving) heads of the phospholipids face outward, while the hydrophobic (water-fearing) tails face inward, creating a barrier that is generally impermeable to large, polar, or charged molecules.

However, specific proteins within the membrane, called channels and transporters, allow certain substances to cross the membrane. Channels are protein structures that span the membrane and provide a pore for ions or small uncharged molecules to pass through. Transporters, on the other hand, are proteins that bind to specific molecules and facilitate their movement across the membrane, often using energy in the form of ATP.

The permeability of the cell membrane can be influenced by various factors, such as temperature, pH, and the presence of certain chemicals or drugs. Changes in permeability can have significant consequences for the cell's function and survival, as they can disrupt ion balances, nutrient uptake, waste removal, and signal transduction.

Vanadates are salts or esters of vanadic acid (HVO3), which contains the vanadium(V) ion. They contain the vanadate ion (VO3-), which consists of one vanadium atom and three oxygen atoms. Vanadates have been studied for their potential insulin-mimetic and antidiabetic effects, as well as their possible cardiovascular benefits. However, more research is needed to fully understand their mechanisms of action and potential therapeutic uses in medicine.

Bradykinin is a naturally occurring peptide in the human body, consisting of nine amino acids. It is a potent vasodilator and increases the permeability of blood vessels, causing a local inflammatory response. Bradykinin is formed from the breakdown of certain proteins, such as kininogen, by enzymes called kininases or proteases, including kallikrein. It plays a role in several physiological processes, including pain transmission, blood pressure regulation, and the immune response. In some pathological conditions, such as hereditary angioedema, bradykinin levels can increase excessively, leading to symptoms like swelling, redness, and pain.

I'm sorry for any confusion, but "Oxazoles" is not a medical term, it is a chemical term. Oxazoles are heterocyclic aromatic organic compounds that contain a five-membered ring made up of one nitrogen atom, one oxygen atom, and three carbon atoms. They have the molecular formula C4H4NO.

Oxazoles do not have specific medical relevance, but they can be found in some natural and synthetic substances, including certain drugs and bioactive molecules. Some oxazole-containing compounds have been studied for their potential medicinal properties, such as anti-inflammatory, antimicrobial, and anticancer activities. However, these studies are primarily within the field of chemistry and pharmacology, not medicine itself.

Nifedipine is an antihypertensive and calcium channel blocker medication. It works by relaxing the muscles of the blood vessels, which helps to lower blood pressure and improve the supply of oxygen and nutrients to the heart. Nifedipine is used to treat high blood pressure (hypertension), angina (chest pain), and certain types of heart rhythm disorders.

In medical terms, nifedipine can be defined as: "A dihydropyridine calcium channel blocker that is used in the treatment of hypertension, angina pectoris, and Raynaud's phenomenon. It works by inhibiting the influx of calcium ions into vascular smooth muscle and cardiac muscle, which results in relaxation of the vascular smooth muscle and decreased workload on the heart."

I believe there may be some confusion in your question. "Rabbits" is a common name used to refer to the Lagomorpha species, particularly members of the family Leporidae. They are small mammals known for their long ears, strong legs, and quick reproduction.

However, if you're referring to "rabbits" in a medical context, there is a term called "rabbit syndrome," which is a rare movement disorder characterized by repetitive, involuntary movements of the fingers, resembling those of a rabbit chewing. It is also known as "finger-chewing chorea." This condition is usually associated with certain medications, particularly antipsychotics, and typically resolves when the medication is stopped or adjusted.

Inositol phosphates are a family of molecules that consist of an inositol ring, which is a six-carbon heterocyclic compound, linked to one or more phosphate groups. These molecules play important roles as intracellular signaling intermediates and are involved in various cellular processes such as cell growth, differentiation, and metabolism.

Inositol hexakisphosphate (IP6), also known as phytic acid, is a form of inositol phosphate that is found in plant-based foods. IP6 has the ability to bind to minerals such as calcium, magnesium, and iron, which can reduce their bioavailability in the body.

Inositol phosphates have been implicated in several diseases, including cancer, diabetes, and neurodegenerative disorders. For example, altered levels of certain inositol phosphates have been observed in cancer cells, suggesting that they may play a role in tumor growth and progression. Additionally, mutations in enzymes involved in the metabolism of inositol phosphates have been associated with several genetic diseases.

A sodium-calcium exchanger (NCX) is a type of ion transport protein found in the membranes of cells, including those of the heart and brain. It plays a crucial role in regulating intracellular calcium concentrations by facilitating the exchange of sodium ions for calcium ions across the cell membrane.

During each heartbeat, calcium ions enter the cardiac muscle cells to trigger contraction. After the contraction, the sodium-calcium exchanger helps remove excess calcium from the cell by exchanging it for sodium ions. This process is essential for maintaining normal calcium levels within the cell and allowing the heart muscle to relax between beats.

There are three main isoforms of the sodium-calcium exchanger (NCX1, NCX2, and NCX3) with different tissue distributions and functions. Dysfunction in sodium-calcium exchangers has been implicated in various pathological conditions such as heart failure, hypertension, and neurological disorders.

Biological transport refers to the movement of molecules, ions, or solutes across biological membranes or through cells in living organisms. This process is essential for maintaining homeostasis, regulating cellular functions, and enabling communication between cells. There are two main types of biological transport: passive transport and active transport.

Passive transport does not require the input of energy and includes:

1. Diffusion: The random movement of molecules from an area of high concentration to an area of low concentration until equilibrium is reached.
2. Osmosis: The diffusion of solvent molecules (usually water) across a semi-permeable membrane from an area of lower solute concentration to an area of higher solute concentration.
3. Facilitated diffusion: The assisted passage of polar or charged substances through protein channels or carriers in the cell membrane, which increases the rate of diffusion without consuming energy.

Active transport requires the input of energy (in the form of ATP) and includes:

1. Primary active transport: The direct use of ATP to move molecules against their concentration gradient, often driven by specific transport proteins called pumps.
2. Secondary active transport: The coupling of the movement of one substance down its electrochemical gradient with the uphill transport of another substance, mediated by a shared transport protein. This process is also known as co-transport or counter-transport.

Purinergic agonists are substances that bind to and activate purinergic receptors, which are a type of cell surface receptor found in many tissues throughout the body. These receptors are activated by endogenous molecules called purines, including adenosine triphosphate (ATP) and uridine triphosphate (UTP), as well as their breakdown products such as adenosine.

Purinergic agonists can have a variety of effects on different tissues, depending on the type of purinergic receptor that they activate. For example, ATP acting as a purinergic agonist can cause smooth muscle contraction, increase heart rate and blood pressure, and modulate neurotransmission in the brain.

Purinergic agonists are used in research to study the functions of purinergic receptors and their roles in various physiological processes. They also have potential therapeutic applications, such as in the treatment of cardiovascular diseases, pain, and neurological disorders. However, it is important to note that the use of purinergic agonists as drugs must be carefully studied and regulated due to their potential for adverse effects.

A cell membrane, also known as the plasma membrane, is a thin semi-permeable phospholipid bilayer that surrounds all cells in animals, plants, and microorganisms. It functions as a barrier to control the movement of substances in and out of the cell, allowing necessary molecules such as nutrients, oxygen, and signaling molecules to enter while keeping out harmful substances and waste products. The cell membrane is composed mainly of phospholipids, which have hydrophilic (water-loving) heads and hydrophobic (water-fearing) tails. This unique structure allows the membrane to be flexible and fluid, yet selectively permeable. Additionally, various proteins are embedded in the membrane that serve as channels, pumps, receptors, and enzymes, contributing to the cell's overall functionality and communication with its environment.

Caspase-12 is a type of protease enzyme that belongs to the family of caspases, which are cysteine-aspartic acid proteases playing essential roles in programmed cell death (apoptosis). Caspase-12 is primarily expressed in the endoplasmic reticulum (ER) and is involved in ER stress-induced apoptosis.

During ER stress, misfolded or unfolded proteins accumulate in the ER lumen, triggering an adaptive response called the unfolded protein response (UPR). If the UPR fails to restore ER homeostasis, caspase-12 is activated and contributes to the initiation of the apoptotic process.

However, it's worth noting that the role of caspase-12 in human apoptosis remains controversial, as some studies suggest its function might be limited or absent in humans compared to other species like mice.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

The Ryanodine Receptor (RyR) is a calcium release channel located on the sarcoplasmic reticulum (SR), a type of endoplasmic reticulum found in muscle cells. It plays a crucial role in excitation-contraction coupling, which is the process by which electrical signals are converted into mechanical responses in muscle fibers.

In more detail, when an action potential reaches the muscle fiber's surface membrane, it triggers the opening of voltage-gated L-type calcium channels (Dihydropyridine Receptors or DHPRs) in the sarcolemma (the cell membrane of muscle fibers). This influx of calcium ions into the cytoplasm causes a conformational change in the RyR, leading to its own opening and the release of stored calcium from the SR into the cytoplasm. The increased cytoplasmic calcium concentration then initiates muscle contraction through interaction with contractile proteins like actin and myosin.

There are three isoforms of RyR: RyR1, RyR2, and RyR3. RyR1 is primarily found in skeletal muscle, while RyR2 is predominantly expressed in cardiac muscle. Both RyR1 and RyR2 are large homotetrameric proteins with a molecular weight of approximately 2.2 million Daltons. They contain multiple domains including an ion channel pore, regulatory domains, and a foot structure that interacts with DHPRs. RyR3 is more widely distributed, being found in various tissues such as the brain, smooth muscle, and some types of neurons.

Dysfunction of these channels has been implicated in several diseases including malignant hyperthermia, central core disease, catecholaminergic polymorphic ventricular tachycardia (CPVT), and certain forms of heart failure.

Intracellular membranes refer to the membrane structures that exist within a eukaryotic cell (excluding bacteria and archaea, which are prokaryotic and do not have intracellular membranes). These membranes compartmentalize the cell, creating distinct organelles or functional regions with specific roles in various cellular processes.

Major types of intracellular membranes include:

1. Nuclear membrane (nuclear envelope): A double-membraned structure that surrounds and protects the genetic material within the nucleus. It consists of an outer and inner membrane, perforated by nuclear pores that regulate the transport of molecules between the nucleus and cytoplasm.
2. Endoplasmic reticulum (ER): An extensive network of interconnected tubules and sacs that serve as a major site for protein folding, modification, and lipid synthesis. The ER has two types: rough ER (with ribosomes on its surface) and smooth ER (without ribosomes).
3. Golgi apparatus/Golgi complex: A series of stacked membrane-bound compartments that process, sort, and modify proteins and lipids before they are transported to their final destinations within the cell or secreted out of the cell.
4. Lysosomes: Membrane-bound organelles containing hydrolytic enzymes for breaking down various biomolecules (proteins, carbohydrates, lipids, and nucleic acids) in the process called autophagy or from outside the cell via endocytosis.
5. Peroxisomes: Single-membrane organelles involved in various metabolic processes, such as fatty acid oxidation and detoxification of harmful substances like hydrogen peroxide.
6. Vacuoles: Membrane-bound compartments that store and transport various molecules, including nutrients, waste products, and enzymes. Plant cells have a large central vacuole for maintaining turgor pressure and storing metabolites.
7. Mitochondria: Double-membraned organelles responsible for generating energy (ATP) through oxidative phosphorylation and other metabolic processes, such as the citric acid cycle and fatty acid synthesis.
8. Chloroplasts: Double-membraned organelles found in plant cells that convert light energy into chemical energy during photosynthesis, producing oxygen and organic compounds (glucose) from carbon dioxide and water.
9. Endoplasmic reticulum (ER): A network of interconnected membrane-bound tubules involved in protein folding, modification, and transport; it is divided into two types: rough ER (with ribosomes on the surface) and smooth ER (without ribosomes).
10. Nucleus: Double-membraned organelle containing genetic material (DNA) and associated proteins involved in replication, transcription, RNA processing, and DNA repair. The nuclear membrane separates the nucleoplasm from the cytoplasm and contains nuclear pores for transporting molecules between the two compartments.

Xanthenes are a class of organic compounds that contain a xanthene core, which is a tricyclic compound made up of two benzene rings fused to a central pyran ring. They have the basic structure:

While xanthenes themselves do not have significant medical applications, many of their derivatives are widely used in medicine and research. For example, fluorescein and eosin are xanthene dyes that are commonly used as diagnostic tools in ophthalmology and as stains in histology. Additionally, some xanthene derivatives have been explored for their potential therapeutic benefits, such as anti-inflammatory, antimicrobial, and anticancer activities. However, it is important to note that individual medical definitions would depend on the specific xanthene derivative in question.

Calcium channel agonists are substances that increase the activity or function of calcium channels. Calcium channels are specialized proteins in cell membranes that regulate the flow of calcium ions into and out of cells. They play a crucial role in various physiological processes, including muscle contraction, hormone secretion, and nerve impulse transmission.

Calcium channel agonists can enhance the opening of these channels, leading to an increased influx of calcium ions into the cells. This can result in various pharmacological effects, depending on the type of cell and tissue involved. For example, calcium channel agonists may be used to treat conditions such as hypotension (low blood pressure) or heart block by increasing cardiac contractility and heart rate. However, these agents should be used with caution due to their potential to cause adverse effects, including increased heart rate, hypertension, and arrhythmias.

Examples of calcium channel agonists include drugs such as Bay K 8644, FPL 64176, and A23187. It's important to note that some substances can act as both calcium channel agonists and antagonists, depending on the dose, concentration, or duration of exposure.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Tetradecanoylphorbol acetate (TPA) is defined as a pharmacological agent that is a derivative of the phorbol ester family. It is a potent tumor promoter and activator of protein kinase C (PKC), a group of enzymes that play a role in various cellular processes such as signal transduction, proliferation, and differentiation. TPA has been widely used in research to study PKC-mediated signaling pathways and its role in cancer development and progression. It is also used in topical treatments for skin conditions such as psoriasis.

Staurosporine is an alkaloid compound that is derived from the bacterium Streptomyces staurosporeus. It is a potent and broad-spectrum protein kinase inhibitor, which means it can bind to and inhibit various types of protein kinases, including protein kinase C (PKC), cyclin-dependent kinases (CDKs), and tyrosine kinases.

Protein kinases are enzymes that play a crucial role in cell signaling by adding phosphate groups to other proteins, thereby modulating their activity. The inhibition of protein kinases by staurosporine can disrupt these signaling pathways and lead to various biological effects, such as the induction of apoptosis (programmed cell death) and the inhibition of cell proliferation.

Staurosporine has been widely used in research as a tool to study the roles of protein kinases in various cellular processes and diseases, including cancer, neurodegenerative disorders, and inflammation. However, its use as a therapeutic agent is limited due to its lack of specificity and high toxicity.

Transcription Factor CHOP, also known as DNA Binding Protein C/EBP Homologous Protein or GADD153 (Growth Arrest and DNA Damage-inducible protein 153), is a transcription factor that is involved in the regulation of gene expression in response to various stress stimuli, such as endoplasmic reticulum (ER) stress, hypoxia, and DNA damage.

CHOP is a member of the C/EBP (CCAAT/enhancer-binding protein) family of transcription factors, which bind to specific DNA sequences called cis-acting elements in the promoter regions of target genes. CHOP can form heterodimers with other C/EBP family members and bind to their target DNA sequences, thereby regulating gene expression.

Under normal physiological conditions, CHOP is expressed at low levels. However, under stress conditions, such as ER stress, the expression of CHOP is upregulated through the activation of the unfolded protein response (UPR) signaling pathways. Once activated, CHOP can induce the transcription of genes involved in apoptosis, cell cycle arrest, and oxidative stress response, leading to programmed cell death or survival, depending on the severity and duration of the stress signal.

Therefore, CHOP plays a critical role in maintaining cellular homeostasis by regulating gene expression in response to various stress stimuli, and its dysregulation has been implicated in several pathological conditions, including neurodegenerative diseases, cancer, and metabolic disorders.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Homeostasis is a fundamental concept in the field of medicine and physiology, referring to the body's ability to maintain a stable internal environment, despite changes in external conditions. It is the process by which biological systems regulate their internal environment to remain in a state of dynamic equilibrium. This is achieved through various feedback mechanisms that involve sensors, control centers, and effectors, working together to detect, interpret, and respond to disturbances in the system.

For example, the body maintains homeostasis through mechanisms such as temperature regulation (through sweating or shivering), fluid balance (through kidney function and thirst), and blood glucose levels (through insulin and glucagon secretion). When homeostasis is disrupted, it can lead to disease or dysfunction in the body.

In summary, homeostasis is the maintenance of a stable internal environment within biological systems, through various regulatory mechanisms that respond to changes in external conditions.

Uridine Triphosphate (UTP) is a nucleotide that plays a crucial role in the synthesis and repair of DNA and RNA. It consists of a nitrogenous base called uracil, a pentose sugar (ribose), and three phosphate groups. UTP is one of the four triphosphates used in the biosynthesis of RNA during transcription, where it donates its uracil base to the growing RNA chain. Additionally, UTP serves as an energy source and a substrate in various biochemical reactions within the cell, including phosphorylation processes and the synthesis of glycogen and other molecules.

Alkaloids are a type of naturally occurring organic compounds that contain mostly basic nitrogen atoms. They are often found in plants, and are known for their complex ring structures and diverse pharmacological activities. Many alkaloids have been used in medicine for their analgesic, anti-inflammatory, and therapeutic properties. Examples of alkaloids include morphine, quinine, nicotine, and caffeine.

Gadolinium is a rare earth metal that is used as a contrast agent in medical imaging techniques such as Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA). It works by shortening the relaxation time of protons in tissues, which enhances the visibility of internal body structures on the images. Gadolinium-based contrast agents are injected into the patient's bloodstream during the imaging procedure.

It is important to note that in some individuals, gadolinium-based contrast agents can cause a condition called nephrogenic systemic fibrosis (NSF), which is a rare but serious disorder that affects people with severe kidney disease. NSF causes thickening and hardening of the skin, joints, eyes, and internal organs. Therefore, it is essential to evaluate a patient's renal function before administering gadolinium-based contrast agents.

Imidazoles are a class of heterocyclic organic compounds that contain a double-bonded nitrogen atom and two additional nitrogen atoms in the ring. They have the chemical formula C3H4N2. In a medical context, imidazoles are commonly used as antifungal agents. Some examples of imidazole-derived antifungals include clotrimazole, miconazole, and ketoconazole. These medications work by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes, leading to increased permeability and death of the fungal cells. Imidazoles may also have anti-inflammatory, antibacterial, and anticancer properties.

Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (CCP) is a chemical compound that functions as an ionophore, which is a type of molecule that can transport ions across biological membranes. CCP is specifically known to transport protons (H+) and has been used in research as a tool to study the role of proton transport in various cellular processes.

CCP is also a potent mitochondrial uncoupler, which means that it disrupts the normal functioning of the mitochondria, the energy-producing structures in cells. By doing so, CCP can cause a rapid and irreversible decline in ATP (adenosine triphosphate) production, leading to cell death.

Due to its potent toxicity, CCP is not used as a therapeutic agent but rather as a research tool to study mitochondrial function and cellular metabolism. It is important to handle this compound with care and follow appropriate safety protocols when working with it in the laboratory.

Calcium channels, L-type, are a type of voltage-gated calcium channel that are widely expressed in many excitable cells, including cardiac and skeletal muscle cells, as well as certain neurons. These channels play a crucial role in the regulation of various cellular functions, such as excitation-contraction coupling, hormone secretion, and gene expression.

L-type calcium channels are composed of five subunits: alpha-1, alpha-2, beta, gamma, and delta. The alpha-1 subunit is the pore-forming subunit that contains the voltage sensor and the selectivity filter for calcium ions. It has four repeated domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment in each domain functions as a voltage sensor, moving outward upon membrane depolarization to open the channel and allow calcium ions to flow into the cell.

L-type calcium channels are activated by membrane depolarization and have a relatively slow activation and inactivation time course. They are also modulated by various intracellular signaling molecules, such as protein kinases and G proteins. L-type calcium channel blockers, such as nifedipine and verapamil, are commonly used in the treatment of hypertension, angina, and certain cardiac arrhythmias.

Econazole is an antifungal medication used to treat various fungal infections of the skin, nails, and mucous membranes. It works by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes, thereby weakening the cell membrane and increasing permeability, ultimately leading to fungal cell death.

Econazole is available in various formulations, including creams, lotions, powders, and tablets. It is commonly used to treat conditions such as athlete's foot, jock itch, ringworm, candidiasis (yeast infection), and other fungal skin infections.

It is important to follow the instructions of a healthcare provider when using econazole or any medication, and to report any side effects or concerns promptly.

Aniline compounds, also known as aromatic amines, are organic compounds that contain a benzene ring substituted with an amino group (-NH2). Aniline itself is the simplest and most common aniline compound, with the formula C6H5NH2.

Aniline compounds are important in the chemical industry and are used in the synthesis of a wide range of products, including dyes, pharmaceuticals, and rubber chemicals. They can be produced by reducing nitrobenzene or by directly substituting ammonia onto benzene in a process called amination.

It is important to note that aniline compounds are toxic and can cause serious health effects, including damage to the liver, kidneys, and central nervous system. They can also be absorbed through the skin and are known to have carcinogenic properties. Therefore, appropriate safety measures must be taken when handling aniline compounds.

"Wistar rats" are a strain of albino rats that are widely used in laboratory research. They were developed at the Wistar Institute in Philadelphia, USA, and were first introduced in 1906. Wistar rats are outbred, which means that they are genetically diverse and do not have a fixed set of genetic characteristics like inbred strains.

Wistar rats are commonly used as animal models in biomedical research because of their size, ease of handling, and relatively low cost. They are used in a wide range of research areas, including toxicology, pharmacology, nutrition, cancer, cardiovascular disease, and behavioral studies. Wistar rats are also used in safety testing of drugs, medical devices, and other products.

Wistar rats are typically larger than many other rat strains, with males weighing between 500-700 grams and females weighing between 250-350 grams. They have a lifespan of approximately 2-3 years. Wistar rats are also known for their docile and friendly nature, making them easy to handle and work with in the laboratory setting.

The extracellular space is the region outside of cells within a tissue or organ, where various biological molecules and ions exist in a fluid medium. This space is filled with extracellular matrix (ECM), which includes proteins like collagen and elastin, glycoproteins, and proteoglycans that provide structural support and biochemical cues to surrounding cells. The ECM also contains various ions, nutrients, waste products, signaling molecules, and growth factors that play crucial roles in cell-cell communication, tissue homeostasis, and regulation of cell behavior. Additionally, the extracellular space includes the interstitial fluid, which is the fluid component of the ECM, and the lymphatic and vascular systems, through which cells exchange nutrients, waste products, and signaling molecules with the rest of the body. Overall, the extracellular space is a complex and dynamic microenvironment that plays essential roles in maintaining tissue structure, function, and homeostasis.

Barium is a naturally occurring, silvery-white metallic chemical element with the symbol Ba and atomic number 56. In medical terms, barium is commonly used as a contrast agent in radiology, particularly in X-ray examinations such as an upper GI series or barium enema. The barium sulfate powder is mixed with water to create a liquid or thick paste that is swallowed or inserted through the rectum. This provides a white coating on the inside lining of the digestive tract, allowing it to be seen more clearly on X-ray images and helping doctors diagnose various conditions such as ulcers, tumors, or inflammation.

It's important to note that barium is not absorbed by the body and does not cause any harm when used in medical imaging procedures. However, if it is accidentally inhaled or aspirated into the lungs during administration, it can cause chemical pneumonitis, a potentially serious condition. Therefore, it should only be administered under the supervision of trained medical professionals.

Ruthenium Red is not a medical term itself, but it is a chemical compound that has been used in some medical research and procedures. Ruthenium Red is a dye that is used as a marker in electron microscopy to stain and highlight cellular structures, particularly mitochondria, the energy-producing organelles of cells. It can also be used in experimental treatments for conditions such as heart failure and neurodegenerative diseases.

In summary, Ruthenium Red is a chemical compound with potential medical applications as a research tool and experimental treatment, rather than a standalone medical condition or diagnosis.

Cell compartmentation, also known as intracellular compartmentalization, refers to the organization of cells into distinct functional and spatial domains. This is achieved through the separation of cellular components and biochemical reactions into membrane-bound organelles or compartments. Each compartment has its unique chemical composition and environment, allowing for specific biochemical reactions to occur efficiently and effectively without interfering with other processes in the cell.

Some examples of membrane-bound organelles include the nucleus, mitochondria, chloroplasts, endoplasmic reticulum, Golgi apparatus, lysosomes, peroxisomes, and vacuoles. These organelles have specific functions, such as energy production (mitochondria), protein synthesis and folding (endoplasmic reticulum and Golgi apparatus), waste management (lysosomes), and lipid metabolism (peroxisomes).

Cell compartmentation is essential for maintaining cellular homeostasis, regulating metabolic pathways, protecting the cell from potentially harmful substances, and enabling complex biochemical reactions to occur in a controlled manner. Dysfunction of cell compartmentation can lead to various diseases, including neurodegenerative disorders, cancer, and metabolic disorders.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

... treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. Thapsigargin is useful ... Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). Structurally, thapsigargin ... Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into ... A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. The ...
The chemical compound thapsigargin has been isolated from Thapsia garganica. A synthetic prodrug of thapsigargin called "G-202 ... This same chemical compound thapsigargin is now being looked at as an antiviral to use against SARS-coV-2, the coronavirus ... in San Antonio, TX is studying methods of delivering thapsigargin directly to cancer cells, avoiding damage to other cells in ... "Thapsigargin prodrug G-202". NCI Cancer Dictionary. Kristen Philipkoski (2 February 2012). "Scientists Transform Deadly Plant ...
An example of a Grob-like fragmentation in organic synthesis is the expansion of the Wieland-Miescher ketone to thapsigargin: ... "Synthesis of the thapsigargins". Proceedings of the National Academy of Sciences. 101 (33): 12073-12078. Bibcode:2004PNAS.. ...
Thapsigargin coated intraocular lenses inhibit human lens cell growth. Nature Medicine: 3, 1028-1030. DX Xie, BF Feys, S James ...
It is a thapsigargin-based prodrug with cytotoxic activity used to reduce blood flow to the tumor during treatment. Results ... phyton (2016-08-22). "Phyton Biotech Achieves Manufacturing Milestone with Thapsigargin, the Active Agent in Mipsagargin". ...
For experimental purposes, SERCA can be inhibited by thapsigargin and induced by istaroxime. SERCA function is upregulated in ...
... increases agonist and thapsigargin releasable Ca2+ storage in the Golgi". The Journal of Cell Biology. 145 (2): 279-89. doi: ...
CPA also binds to SERCA ATPase at the same site as another inhibitor, thapsigargin (TG). In this way, CPA lowers the ability of ... for thapsigargin and cyclopiazonic acid". Biochemistry. 38 (47): 15522-7. doi:10.1021/bi991523q. PMID 10569935. Voss KA (May ...
... thapsigargin, arsenite and heat-shock treatments". Experimental Cell Research. 315 (6): 968-80. doi:10.1016/j.yexcr.2009.01.012 ...
... thapsigargin, arsenite and heat-shock treatments". Experimental Cell Research. 315 (6): 968-980. doi:10.1016/j.yexcr.2009.01. ... thapsigargin), proteasome inhibition (MG132), hyperosmotic stress, ultraviolet radiation, inhibition of eIF4A (pateamine A, ...
... can reduce calcium influx through inhibition of the fMLP, AlF4−, and thapsigargin G-protein pathways. Honokiol has ...
... thapsigargin leads to ER Ca2+ depletion due to inhibition of the Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA). A23187 ...
This is effected by its inhibiting thrombin and thapsigargin, two activators of SOCE that increase intracellular free calcium. ...
Catalyzed Allenic Pauson-Khand Reaction to Access the Thapsigargin Core: Influence of Furan and Allenyl Chloroacetate Groups on ... which enable the enantioselective synthesis of compounds such as thapsigargin. Her approach includes collaborations with ...
Ca2+ uptake usually occurs via a thapsigargin-insensitive pathway (therefore precluding SERCA involvement) and appears to be ... thapsigargin). This is a blanket term that encompasses a spectrum of acidic vesicles that include endosomes, lysosomes, and ... thapsigargin) whereas the exchanger exploit the H+ gradient to drive Ca2+ uptake against its concentration gradient. The genes ...
Thapsigargin kills cells irrespective of the rate of cell division, which may provide an effective approach to kill both fast- ... The objective of the collaboration was to chemically alter thapsigargin to a derivative that could be linked to peptides, thus ... The active ingredient in G-202 is a chemotherapeutic agent derived from thapsigargin, a plant-based cytotoxin that kills by ... GenSpera's prodrug delivery system keeps the thapsigargin inactive in the body until it finds cells that it has been programmed ...
... thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1". Molecular and Cellular Biology. 20 (14): ...
... thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1". Mol. Cell. Biol. 20 (14): 5096-106. doi: ... Thapsigargin Stress-Induced Changes and Synergistic Interactions with NF-Y and YY1". Mol. Cell. Biol. 20 (14): 5096-106. doi: ...
Their effects are mimicked by the pharmacological agent, thapsigargin, which is sometimes used in fluid secretion assays when a ...
TcK6 causes modest suppression of thapsigargin-triggered IFN-g production by sheep T cells, suggesting that the parasite use ...
... and both are inhibited by the tumor-promoting agent thapsigargin, which does not affect the plasma membrane Ca2+ pumps. Active ...
Thapsigargin, cyclopamine, Thiostrepton, Staurosporine, Mithramycin, Midostaurin, Wortmannin, K252a, Geldanamycin and its ...
Thapsigargin, a sesquiterpene lactone and tumor promoter Thyroglobulin, a protein Transgenic, referring to genetic material ...
... thapsigargin MeSH D02.455.849.765.850 - trichothecenes MeSH D02.455.849.765.850.870 - t-2 toxin MeSH D02.455.849.765.850.900 - ...
Tetracycline Thapsigargin Thaumatin Thiamine (vitamin B1) - C12H17ClN4OS·HCl Threonine Thrombopoietin Thromboxane Thymidine ...
One of these prodrugs termed G202 consists of an analog of the highly toxic natural product thapsigargin coupled to a peptide ...
... thapsigargin, epothilone A, antascomicin B, bengazole A and rapamycin. His total synthesis of azadirachtin, completed in 2007, ...
The addition of thapsigargin (the SERCA pump inhibitor that stimulates SOCE by passive depletion of intracellular Ca2+ stores) ...
... and 3 to thapsigargin and other inhibitors". J. Biol. Chem. 281 (11): 6970-6. doi:10.1074/jbc.M510978200. PMID 16410239. ...
Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. Thapsigargin is useful ... Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). Structurally, thapsigargin ... Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into ... A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. The ...
A) Cells expressing PrP were incubated with thapsigargin for 0 (lanes 1C2) or 230 min (lanes 3C4) and then pulsed for 10 min in ... A) Cells expressing PrP were incubated with thapsigargin for 0 (lanes 1C2) or 230 min (lanes 3C4) and then pulsed for 10 min in ... the presence of thapsigargin. by fabretpPosted on. February 19, 2023. ... the presence of thapsigargin. and may be important for its propagation. strong class="kwd-title" Key Words: Ca2+ homeostasis, ...
... is a nonactive analogue of Thapsigargin from Alomone Labs. A natural & biologically active compound. Lyophilized. Global ... Thapsigargin Epoxide is a non-active analogue of Thapsigargin and can be used as a negative control for Thapsigargin activity9, ... Thapsigargin epoxide is a non-active analogue of Thapsigargin.. References-Activity. *Norup, E. et al. (1986) Planta. Med. 4, ... Thapsigargin, derived from the plant genus Thapsia1,2, is an extremely tight-binding inhibitor of intracellular Ca2+ pumps. It ...
Tunicamycin Ready Made Solution (5mg/mL DMSO, Streptomyces sp.); Tunicamycin was first isolated from Streptomyces lysosuperificus based on its antiviral activity; Tunicamycin is an antibacterial and antifungal; Tunicamycin is an antibacterial and antifungal;
We found that thapsigargin discriminates between low- and high-voltage-activated Ca2+ channels: 2000 nM of thapsigargin ... We found that thapsigargin discriminates between low- and high-voltage-activated Ca2+ channels: 2000 nM of thapsigargin ... We found that thapsigargin discriminates between low- and high-voltage-activated Ca2+ channels: 2000 nM of thapsigargin ... We found that thapsigargin discriminates between low- and high-voltage-activated Ca2+ channels: 2000 nM of thapsigargin ...
thapsigargin. TRAP. thrombin receptor-activating peptide. Amino acids are abbreviated by their one-letter or three-letter codes ... Thapsigargin (TG) was from Sigma (St. Louis, MO).. Evaluation of Receptor Desensitization and Cross-Desensitization of PAR1 and ...
Thapsigargin. Joshi AD, Carter DE, Harper TA, Elferink CJ. 2015. Aryl hydrocarbon receptor-dependent stanniocalcin 2 induction ...
Effects of thapsigargin, an inhibitor of Ca2+-ATPase in surface of endoplasmic reticulum, on apoptotic cell death were studied ... Propidium iodide staining and flow cytometry revealed that in the serum-free condition, thapsigargin increased the rate of ... supporting that thapsigargin is a potent activator of apoptosis in the cells. ...
Thapsigargin, Tumor Cells, Cultured. in Proceedings of the National Academy of Sciences. volume. 92. issue. 17. pages. 5 pages ... Thapsigargin; Tumor Cells, Cultured}}, language = {{eng}}, month = {{08}}, number = {{17}}, pages = {{8064--8068}}, publisher ...
1992) Thapsigargin blocks the induction of long-term potentiation in rat hippocampal slices. Neurosci Lett 139:197-200. ...
The amplitude of thapsigargin-induced calcium currents in HD76 neurons after 24 h incubation with 300 nM EVP4593 was 1.32 ± ... After a 3-s baseline read, we added to the microplate 1 μM of thapsigargin (Sigma, USA) prepared in HBSS buffer containing 2 or ... A) Normalized SOC currents evoked by application of thapsigargin (1 μM) and plotted as a function of time in HD76 (red circles ... We showed that the peak amplitude of thapsigargin-induced calcium currents was 3.01 ± 0.19 pA/pF in HD76 neurons compared to ...
Ti(II) and Rh(I) Complexes as Reagents toward a Thapsigargin Core. Sanogo Y, Othman RB, Dhambri S, Selkti M, Jeuken A, Prunet J ...
Synthesis of the thapsigargins. Proc Natl Acad Sci U S A. 2004 Aug 17; 101(33):12073-8. ...
We showed that passive endoplasmic reticulum (ER) depletion by thapsigargin or cell stimulation by histamine activated a ...
... in comparison to that of thapsigargin (orange), is reported in panel (b). The interacting residues of the protein have been ... in comparison to that of thapsigargin (orange), is reported in panel (b). The interacting residues of the protein have been ... which outperforms the one obtained for the thapsigargin, the molecule used as positive control (−8.4 kcal/mol). Compound 4 ... fitted within the identified binding pocket only partially sharing a similar interaction motif with respect to thapsigargin ( ...
BAPTA-AM, thapsigargin and U73122 hyperpolarized SMCs, relaxed the vessel, decreased basal calcium levels and abolished ...
2011) Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest Molecular Cell 42: ...
How would this property affect Bip oligomerization during sudden change in ER ionic strength, such as thapsigargin-mediated ... 1993) Inhibition of protein synthesis and early protein processing by thapsigargin in cultured cells The Biochemical Journal ... Note: To promote BiP oligomerization in vivo, the CHO-K1 cells in panels B-D were treated with thapsigargin (0.5 µM for 10 min ... C) As in A, substituting the calcium ionophore A23187 (A23, 10 µM) for thapsigargin. (D) As in B substituting the calcium ...
The number of such granules increased with thapsigargin treatment, confirming that the granules were stress granules. Given ...
Induction of ER stress with thapsigargin converts human neutrophils to immune-suppressive PMN-MDSCs (9). CHOP is implicated in ...
Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular ... Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular ... In contrast, co-treatment with the classical GRP inducers thapsigargin and tunicamycin produced only simple additive increases ...
... after thapsigargin treatment. The thapsigargin-releasable pool of ER Ca2+ was depleted in cells expressing Bak-cb5 (Fig. 5 A). ... Immortalized wild-type and bax−/−bak−/− MEFs and NIH3T3 cells were treated with brefeldin A (BFA; 10 μg/ml), thapsigargin (Thap ... Immortalized wild-type and bax−/−bak−/− MEFs and NIH3T3 cells were treated with brefeldin A (BFA; 10 μg/ml), thapsigargin (Thap ... 5 A). To demonstrate that the abolishment of the thapsigargin-inducible [Ca2+]i spike is due to the depletion of the ER Ca2+ ...
The treatments were done with ER stress inducers thapsigargin and tunicamycin, and with IRE1 inhibitors KIRA6 and 4μ8c, or the ... qPCR revealed that the other observed UPR markers were activated as well upon thapsigargin treatment, however, they were not ...
UPR activation with thapsigargin increases human induced pluripotent stem cell beta cell HLA Class I antigen presentation to ...
Authi, KS, Bokkala, S, Patel, Y, Kakkar, VV, Munkonge, F. Ca2+ release from platelet intracellular stores by thapsigargin and 2 ...
Topical application of thapsigargin, which inhibits the ER Ca(2+) ATPase activity without compromising barrier integrity, also ...
2, pretreatment with 1 μmol/l thapsigargin for 10 min reduced the L-783,281-induced [Ca2+]i change by 82 ± 4% (n = 6 cells, P ... Thapsigargin has been shown to deplete intracellular Ca2+ stores by inhibiting sarco/endoplasmic reticulum Ca2+-ATPases (34). ... To determine if the rise in [Ca2+]i was associated with release from intracellular Ca2+ stores, the effect of thapsigargin was ... Our data indicate that the majority of the [Ca2+]i increase that occurs during application of L-783,281 comes from thapsigargin ...
The in vitro effects of nicotine and selected antibiotics, tunicamycin and thapsigargin on human Breast carcinoma (mcf-7) cells ...
Lentine, K. L., Lam, N. N., Naik, A. S., Axelrod, D. A., Zhang, Z., Dharnidharka, V. R., Hess, G. P., Segev, D. L., Ouseph, R., Randall, H., Alhamad, T., Devraj, R., Gadi, R., Kasiske, B. L., Brennan, D. C. & Schnitzler, M. A., Dec 2018, In: American Journal of Transplantation. 18, 12, p. 2987-2999 13 p.. Research output: Contribution to journal › Article › peer-review ...
  • To raised understand the part that Asp421 cleaved tau may play in facilitating neuronal death related to ER stress we examined immortalized cortical neurons that inducibly express either a full-length form of tau (T4) or a tau isoform that has been pseudo-truncated at Asp421 (T4C3) in response to thapsigargin treatment. (immune-source.com)
  • Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. (wikipedia.org)
  • Activity Thapsigargin is an extremely tight-binding inhibitor of intracellular Ca 2+ pumps, but initially described as a tumor promoting agent which induces rapid Ca 2+ release from intracellular stores 1 . (alomone.com)
  • Thapsigargin , derived from the plant genus Thapsia 1,2 , is an extremely tight-binding inhibitor of intracellular Ca 2+ pumps. (alomone.com)
  • The action of thapsigargin on intracellular calcium homeostasis and voltage-activated calcium currents was studied on freshly isolated adult mouse dorsal root ganglia neurons. (uaeu.ac.ae)
  • However, 5-10 min incubation of neurons with 20 nM thapsigargin completely and almost irreversibly inhibited caffeine-mediated Ca 2+ release from intracellular pools. (uaeu.ac.ae)
  • In addition, the effects were abolished by inhibitors of two intracellular calcium release channels: 2-APB, an inhibitor of inositol trisphosphate receptors, and dantrolene, an inhibitor of ryanodine receptors, but not by thapsigargin, an inhibitor of endoplasmic reticulum calcium uptake. (nih.gov)
  • Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
  • Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. (wikipedia.org)
  • Thapsigargin is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations and ER calcium depletion. (wikipedia.org)
  • Thapsigargin-induced depletion of Ca 2+ stores causes apoptosis in most cell lines 5 . (alomone.com)
  • We showed that passive endoplasmic reticulum (ER) depletion by thapsigargin or cell stimulation by histamine activated a similar Ca(2+)-release-activated Ca(2+) current (CRAC)-like current when 10 mM Ba(2+)/2 mM Ca(2+) was present in the extracellular solution. (unige.ch)
  • Since inhibition of SERCA is a mechanism of action that has been used to target solid tumors, thapsigargin has attracted research interest. (wikipedia.org)
  • The biological activity has also attracted research into the laboratory synthesis of thapsigargin. (wikipedia.org)
  • Synthesis of the thapsigargins. (harvard.edu)
  • DACT appeared to cause a selective decrease in caffeine-sensitive ryanodine receptor-operated calcium stores in LbetaT2 cells, rather than in thapsigargin-sensitive ER calcium stores. (cdc.gov)
  • Preclinical studies demonstrated that other effects of thapsigargin include suppression of nicotinic acetylcholine receptors activity in neurons of the guinea-pig ileum submucous plexus and rat superior cervical ganglion. (wikipedia.org)
  • Extracellular applications of thapsigargin at concentrations of 20-2000 nM did not cause substantial changes of basal [Ca 2+ ] i level in the majority of neurons studied. (uaeu.ac.ae)
  • Shmigol, A , Kostyuk, P & Verkhratsky, A 1995, ' Dual action of thapsigargin on calcium mobilization in sensory neurons: Inhibition of Ca 2+ uptake by caffeine-sensitive pools and blockade of plasmalemmal Ca 2+ channels ', Neuroscience , vol. 65, no. 4, pp. 1109-1118. (uaeu.ac.ae)
  • The in vitro effects of nicotine and selected antibiotics, tunicamycin and thapsigargin on human Breast carcinoma (mcf-7) cells. (uwc.ac.za)
  • Pursuing AMG 073 (Cinacalcet) long-term treatment with thapsigargin cells expressing T4C3 offered a marked upsurge in cell toxicity underscored by differential activation of caspase-3 in comparison with cells expressing T4. (immune-source.com)
  • Thapsigargin is a drug known to induce ER stress AMG 073 (Cinacalcet) following long-term exposure to cells (Shelton et al. (immune-source.com)
  • Ca2+ uptake and release properties of a thapsigargin-insensitive nonmitochondrial Ca2+ store in A7r5 and 16HBE14o- cells. (ac.be)
  • A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
  • qPCR revealed that the other observed UPR markers were activated as well upon thapsigargin treatment, however, they were not decreased with the treatment with IRE1 specific inhibitors. (helsinki.fi)
  • Un-treated (-) and treated (+, Thapsigargin treatment for 12hrs and 24hrs) HepG2 whole cell extracts (30 μg) were separated by 10% SDS-PAGE, and the membrane was blotted with NDP52 antibody (GTX115378) diluted by 1:2000. (genetex.com)
  • The treatments were done with ER stress inducers thapsigargin and tunicamycin, and with IRE1 inhibitors KIRA6 and 4μ8c, or the combination of those. (helsinki.fi)
  • Analysis of leak in the presence of 25μM thapsigargin and 6muM ruthenium red indicates a simple linear relationship between [Ca2+]SR and the rate of Ca2+ leak. (gla.ac.uk)
  • It is not known whether the secondary modifications to the guaianolide occur before, or after the formation of thapsigargin, but will need to be considered when elucidating the true biosynthesis. (wikipedia.org)
  • Thapsigargin Epoxide is a non-active analogue of Thapsigargin and can be used as a negative control for Thapsigargin activity 9,10 . (alomone.com)
  • Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
  • Thapsigargin (TG) is a potent inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases (SERCAs). (nih.gov)
  • Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain. (nih.gov)
  • Tunicamycin, thapsigargin, or brefeldin A was used to induce ER stress. (aspetjournals.org)
  • It has been shown that MANF plays an important role in protecting cells against tunicamycin and thapsigargin-induced cell death. (topsan.org)
  • Dig2, a murine Scylla/Charybdis homolog, is also a stress-responsive protein induced by a variety of treatments including dexamethasone, thapsigargin, tunicamycin, and heat shock (Wang, 2003). (sdbonline.org)
  • Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. (wikipedia.org)
  • Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. (wikipedia.org)
  • Thapsigargin is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations and ER calcium depletion. (wikipedia.org)
  • Differentiated human neuroblastoma SH-SY5Y cells were injured using the calcium agonist thapsigargin. (medscape.com)
  • Approximately 15% of the total A23187-releasable microsomal calcium store is insensitive to thapsigargin concentrations up to 100 microM. (nih.gov)
  • DACT appeared to cause a selective decrease in caffeine-sensitive ryanodine receptor-operated calcium stores in LbetaT2 cells, rather than in thapsigargin-sensitive ER calcium stores. (cdc.gov)
  • Similarly, receptor-independent thapsigargin-induced calcium influx and IL-8 production were augmented with KDv1 compared to scrambled control. (nih.gov)
  • Degranulation and IL-8 production induced by thapsigargin were inhibited following KDv2 treatment but no difference was evident with calcium influx or PGD2 release. (nih.gov)
  • A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
  • 1. Mipsagargin: The Beginning-Not the End-of Thapsigargin Prodrug-Based Cancer Therapeutics. (nih.gov)
  • 4. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours. (nih.gov)
  • 9. Thapsigargin--from Thapsia L. to mipsagargin. (nih.gov)
  • Transgenic overexpression of regucalcin leads to suppression of thapsigargin- and actinomycin D-induced apoptosis in the testis by modulation of apoptotic pathways. (implen.cn)
  • In the present study, we examined whether dexmedetomidine exerts inhibitory effects on apoptosis mediated by thapsigargin-induced ER-stress in SH-SY5Y cells, and proposed a possible underlying mechanism for its neuroprotective effects. (aimspress.com)
  • These agents also lessened the degree of thapsigargin-induced apoptosis. (medscape.com)
  • 17. Bcl-2 and Bcl-X(L) block thapsigargin-induced nitric oxide generation, c-Jun NH(2)-terminal kinase activity, and apoptosis. (nih.gov)
  • Solid-phase synthesis protocols were developed for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavable by human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavable by prostate-specific membrane antigen. (ku.dk)
  • 11. Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrug. (nih.gov)
  • 12. Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. (nih.gov)
  • Marked regional differences occur in Ca2+ transport rates and sensitivity to both thapsigargin and IP3. (nih.gov)
  • The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. (scienceopen.com)
  • Since inhibition of SERCA is a mechanism of action that has been used to target solid tumors, thapsigargin has attracted research interest. (wikipedia.org)
  • In the presence of atipamezole or efaroxan, but not BU99006, inhibition of eIF2α phosphorylation and CHOP expression significantly increased following treatment with dexmedetomidine in thapsigargin-treated cells. (aimspress.com)
  • ATP dependent Ca2+ accumulation into oxalate-loaded rat brain microsomes is potently inhibited by thapsigargin with an IC50 of 2 nM and maximal inhibition at 10 nM. (nih.gov)
  • 3. Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells. (nih.gov)
  • The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. (worktribe.com)
  • The key features based on cell and animal studies, which make thapsigargin a promising antiviral are that it is effective against viral infection when used before or during an active infection," the researchers said. (newsbytesapp.com)
  • Preclinical studies demonstrated that other effects of thapsigargin include suppression of nicotinic acetylcholine receptors activity in neurons of the guinea-pig ileum submucous plexus and rat superior cervical ganglion. (wikipedia.org)
  • Thapsigargin resistance in human prostate cancer cells. (nih.gov)
  • Any process that modulates the frequency, rate or extent of cellular response to thapsigargin. (planteome.org)
  • Link to all direct and indirect annotations to obsolete regulation of cellular response to thapsigargin. (planteome.org)
  • It is not known whether the secondary modifications to the guaianolide occur before, or after the formation of thapsigargin, but will need to be considered when elucidating the true biosynthesis. (wikipedia.org)
  • Neuroprotective Effects of Dexmedetomidine against Thapsigargin-induced ER-stress via Activity of α2-adrenoceptors and Imidazoline Receptors[J]. AIMS Neuroscience, 2016, 3(2): 237-252. (aimspress.com)
  • Its effects are non-additive with thapsigargin suggesting that the IP3-sensitive Ca2+ pool is a subset of the thapsigargin sensitive Ca2+ pool. (nih.gov)
  • Given that future pandemics are likely to be of animal origin, where animal to human (zoonotic) and reverse zoonotic spread take place, a new generation of antivirals, such as thapsigargin, could play a key role in the control and treatment of important viral infections in both humans and animals," Chang added. (newsbytesapp.com)
  • Palmitate had no effect on mitochondria Ca 2+ uptake or on the Ca 2+ leak rate induced by the addition of 3 j.iM thapsigargin. (psu.edu)
  • 7. Thapsigargin-From Traditional Medicine to Anticancer Drug. (nih.gov)