Adenylate cyclase. Medical search

An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.

One of the virulence factors produced by virulent BORDETELLA organisms. It is a bifunctional protein with both ADENYLYL CYCLASES and hemolysin components.

An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3.

An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.

An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.

A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.

Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.

A multi-function neuropeptide that acts throughout the body by elevating intracellular cyclic AMP level via its interaction with PACAP RECEPTORS. Although first isolated from hypothalamic extracts and named for its action on the pituitary, it is widely distributed in the central and peripheral nervous systems. PACAP is important in the control of endocrine and homeostatic processes, such as secretion of pituitary and gut hormones and food intake.

Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.

Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.

Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.

An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.

A source of inorganic fluoride which is used topically to prevent dental caries.

A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.

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.

One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.

Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.

A species of gram-negative, aerobic bacteria that is the causative agent of WHOOPING COUGH. Its cells are minute coccobacilli that are surrounded by a slime sheath.

A potent vasodilator agent that increases peripheral blood flow.

One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.

The rate dynamics in chemical or physical systems.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.

Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.

An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.

A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES

Nucleotides in which the base moiety is substituted with one or more sulfur atoms.

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite.

A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).

A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)

The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.

N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.

Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.

A highly selective and specific beta antagonist that is used to characterize beta-adrenoceptors.

Large woodland game BIRDS in the subfamily Meleagridinae, family Phasianidae, order GALLIFORMES. Formerly they were considered a distinct family, Melegrididae.

Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.

Hydrogenated alprenolol derivative where the extra hydrogens are often tritiated. This radiolabeled form of ALPRENOLOL, a beta-adrenergic blocker, is used to label the beta-adrenergic receptor for isolation and study.

Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.

A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with LIDOCAINE injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring.

Cell surface proteins that bind pituitary hormones with high affinity and trigger intracellular changes influencing the behavior of cells. Since many pituitary hormones are also released by neurons as neurotransmitters, these receptors are also found in the nervous system.

A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)

Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.

Alcohols derived from the aryl radical (C6H5CH2-) and defined by C6H5CHOH. The concept includes derivatives with any substituents on the benzene ring.

A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.

A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.

Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)

Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.

Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.

A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.

A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)

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 nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.

A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.

One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.

Cell surface proteins that bind VASOACTIVE INTESTINAL PEPTIDE; (VIP); with high affinity and trigger intracellular changes which influence the behavior of cells.

Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.

A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.

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.

Established cell cultures that have the potential to propagate indefinitely.

The relationship between the dose of an administered drug and the response of the organism to the drug.

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.

A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.

A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.

Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.

Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Inhibitor of phosphodiesterases.

A phenothiazine used in the treatment of PSYCHOSES. Its properties and uses are generally similar to those of CHLORPROMAZINE.

The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.

Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.

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.

A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.

Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

Drugs that selectively bind to and activate beta-adrenergic receptors.

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)

A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.

The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.

One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.

Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.

A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.

A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.

The sum of the weight of all the atoms in a molecule.

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.

A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.

A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.

Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.

An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of EPOPROSTENOL, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation.

Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.

A family of G-protein-coupled receptors that share significant homology with GLUCAGON RECEPTORS. They bind PITUITARY ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE with high affinity and trigger intracellular changes that influence the behavior of CELLS.

A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.

Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.

Esters formed between the aldehydic carbon of sugars and the terminal phosphate of adenosine diphosphate.

Gonadal interstitial or stromal cell neoplasm composed of only LEYDIG CELLS. These tumors may produce one or more of the steroid hormones such as ANDROGENS; ESTROGENS; and CORTICOSTEROIDS. Clinical symptoms include testicular swelling, GYNECOMASTIA, sexual precocity in children, or virilization (VIRILISM) in females.

Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).

A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.

The porcine antidiuretic hormone (VASOPRESSINS). It is a cyclic nonapeptide that differs from ARG-VASOPRESSIN by one amino acid, containing a LYSINE at residue 8 instead of an ARGININE. Lys-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.

Elements of limited time intervals, contributing to particular results or situations.

A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.

A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.

A pituitary adenylate cyclase-activating peptide receptor subtype found in LYMPHOCYTES. It binds both PACAP and VASOACTIVE INTESTINAL PEPTIDE and regulates immune responses.

One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.

A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).

Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.

Cell surface proteins that bind gastrointestinal hormones with high affinity and trigger intracellular changes influencing the behavior of cells. Most gastrointestinal hormones also act as neurotransmitters so these receptors are also present in the central and peripheral nervous systems.

Specific, characterizable, poisonous chemicals, often PROTEINS, with specific biological properties, including immunogenicity, produced by microbes, higher plants (PLANTS, TOXIC), or ANIMALS.

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.

An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).

A peptide hormone of about 27 amino acids from the duodenal mucosa that activates pancreatic secretion and lowers the blood sugar level. (USAN and the USP Dictionary of Drug Names, 1994, p597)

The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.

Cell surface proteins that bind cyclic AMP with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized cyclic AMP receptors are those of the slime mold Dictyostelium discoideum. The transcription regulator CYCLIC AMP RECEPTOR PROTEIN of prokaryotes is not included nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.

Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.

Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

Organic or inorganic compounds that contain the -N3 group.

The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.

A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.

A class of cellular membrane receptors that either have an intrinsic guanylate cyclase activity or are closely coupled to specific guanylate cyclases within the cell.

A 27-amino acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exact amino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is found in the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.

A sulfhydryl reagent that is widely used in experimental biochemical studies.

A pituitary adenylate cyclase-activating polypeptide receptor subtype that binds both PACAP and VASOACTIVE INTESTINAL PEPTIDE. It is found predominately in the BRAIN.

A non-hydrolyzed muscarinic agonist used as a research tool.

Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.

A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.

A purine base and a fundamental unit of ADENINE NUCLEOTIDES.

A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.

Cell surface proteins that bind PARATHYROID HORMONE with high affinity and trigger intracellular changes which influence the behavior of cells. Parathyroid hormone receptors on BONE; KIDNEY; and gastrointestinal cells mediate the hormone's role in calcium and phosphate homeostasis.

Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.

Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.

Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.

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.

Cell surface proteins that bind ATRIAL NATRIURETIC FACTOR with high affinity and trigger intracellular changes influencing the behavior of cells. They contain intrinsic guanylyl cyclase activity.

A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)

Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.

Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.

A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.

One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.

A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.

A hereditary syndrome clinically similar to HYPOPARATHYROIDISM. It is characterized by HYPOCALCEMIA; HYPERPHOSPHATEMIA; and associated skeletal development impairment and caused by failure of response to PARATHYROID HORMONE rather than deficiencies. A severe form with resistance to multiple hormones is referred to as Type 1a and is associated with maternal mutant allele of the ALPHA CHAIN OF STIMULATORY G PROTEIN.

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.

The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)

The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

A glycoprotein hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones (THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.

Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.

A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)

The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively.

A pentose active in biological systems usually in its D-form.

A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols.

The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.

Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.

2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.

Fluids originating from the epithelial lining of the intestines, adjoining exocrine glands and from organs such as the liver, which empty into the cavity of the intestines.

Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.

A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98.

Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).

A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.

Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.

The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.

A general term for various neoplastic diseases of the lymphoid tissue.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.

A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.

The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the ADENOHYPOPHYSEAL HORMONES that regulate vital functions such as GROWTH; METABOLISM; and REPRODUCTION.

A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.

The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.

A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.

Proteins prepared by recombinant DNA technology.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

Cell polarization: chemotaxis gets CRACKing. (1/5304)

An early stage in the establishment of cell polarity during chemotaxis of Dictyostelium dicoideum has been identified by a recent study; the new results also show that the development of cell polarity does not rely upon cytoskeletal rearrangement, and may use a spatial sensing mechanism. (+info)

Probing the function of Bordetella bronchiseptica adenylate cyclase toxin by manipulating host immunity. (2/5304)

We have examined the role of adenylate cyclase-hemolysin (CyaA) by constructing an in-frame deletion in the Bordetella bronchiseptica cyaA structural gene and comparing wild-type and cyaA deletion strains in natural host infection models. Both the wild-type strain RB50 and its adenylate cyclase toxin deletion (DeltacyaA) derivative efficiently establish persistent infections in rabbits, rats, and mice following low-dose inoculation. In contrast, an inoculation protocol that seeds the lower respiratory tract revealed significant differences in bacterial numbers and in polymorphonuclear neutrophil recruitment in the lungs from days 5 to 12 postinoculation. We next explored the effects of disarming specific aspects of the immune system on the relative phenotypes of wild-type and DeltacyaA bacteria. SCID, SCID-beige, or RAG-1(-/-) mice succumbed to lethal systemic infection following high- or low-dose intranasal inoculation with the wild-type strain but not the DeltacyaA mutant. Mice rendered neutropenic by treatment with cyclophosphamide or by knockout mutation in the granulocyte colony-stimulating factor locus were highly susceptible to lethal infection by either wild-type or DeltacyaA strains. These results reveal the significant role played by neutrophils early in B. bronchiseptica infection and by acquired immunity at later time points and suggest that phagocytic cells are a primary in vivo target of the Bordetella adenylate cyclase toxin. (+info)

Adenoviral gene transfer of the human V2 vasopressin receptor improves contractile force of rat cardiomyocytes. (3/5304)

BACKGROUND: In congestive heart failure, high systemic levels of the hormone arginine vasopressin (AVP) result in vasoconstriction and reduced cardiac contractility. These effects are mediated by the V1 vasopressin receptor (V1R) coupled to phospholipase C beta-isoforms. The V2 vasopressin receptor (V2R), which promotes activation of the Gs/adenylyl cyclase system, is physiologically expressed in the kidney but not in the myocardium. Expression of a recombinant V2R (rV2R) in the myocardium could result in a positive inotropic effect via the endogenous high concentrations of AVP in heart failure. METHODS AND RESULTS: A recombinant adenovirus encoding the human V2R (Ad-V2R) was tested for its ability to modulate the cardiac Gs/adenylyl cyclase system and to potentiate contractile force in rat ventricular cardiomyocytes and in H9c2 cardiomyoblasts. Ad-V2R infection resulted in a virus concentration-dependent expression of the transgene and led to a marked increase in cAMP formation in rV2R-expressing cardiomyocytes after exposure to AVP. Single-cell shortening measurements showed a significant agonist-induced contraction amplitude enhancement, which was blocked by the V2R antagonist, SR 121463A. Pretreatment of Ad-V2R-infected cardiomyocytes with AVP led to desensitization of the rV2R after short-term agonist exposure but did not lead to further loss of receptor function or density after long-term agonist incubation, thus demonstrating resistance of the rV2R to downregulation. CONCLUSIONS: Adenoviral gene transfer of the V2R in cardiomyocytes can modulate the endogenous adenylyl cyclase-signal transduction cascade and can potentiate contraction amplitude in cardiomyocytes. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in congestive heart failure by bypassing the desensitized beta-adrenergic receptor signaling. (+info)

Kinetic analysis of drug-receptor interactions of long-acting beta2 sympathomimetics in isolated receptor membranes: evidence against prolonged effects of salmeterol and formoterol on receptor-coupled adenylyl cyclase. (4/5304)

The long-acting beta2 sympathomimetics salmeterol and formoterol have been presumed to exert their prolonged action either by binding to an accessory binding site ("exo-site") near the beta2 adrenoceptor or by their high affinity for beta2 adrenoceptors and correspondingly slow dissociation. Whereas most studies with salmeterol had been done in intact tissues, which have slow diffusion and compartmentation of drugs in lipophilic phases, that restrict drug access to the receptor biophase, we used purified receptor membranes from rat lung and disaggregated calf tracheal myocytes as model systems. Binding experiments were designed to measure the slow dissociation of agonists by means of delayed association of (-)-[125I]iodopindolol. Rat lung membranes were pretreated with high concentrations of agonists (salmeterol, formoterol, isoprenaline) before dissociation was induced by 50-fold dilution. Half-times of association of (-)-[125I]iodopindolol remained unchanged compared with untreated controls, indicating that dissociation of agonists occurred in less than 2 min. Adenylyl cyclase experiments were designed to determine the on and off kinetics of agonists to beta2 adrenoceptors by measuring the rate of receptor-induced cyclic AMP (cAMP) formation. Experiments were performed in tracheal membranes characterized by high Vmax values of cAMP formation. Adenylyl cyclase activation occurred simultaneously with the addition of the agonist, continued linearly with time for 60 min, and ceased immediately after the antagonist was added. Similarly, when receptor membranes were preincubated in a small volume with high salmeterol concentrations, there was a linear increase in cAMP formation, which was immediately interrupted by a 100-fold dilution of the reaction mixture. This militates against the exo-site hypothesis. On the other hand, dissociation by dilution was much less when membranes were preincubated with a large volume of salmeterol at the same concentration, indicating that physicochemical effects, and not exo-site binding, underlie its prolonged mode of action. (+info)

Biochemical and cytochemical studies on adenylate cyclase activity in the developing rat submandibular gland: differentiation of of the acinar secretory compartment. (5/5304)

To investigate membrane changes in development of the exocrine cells of the rat submandibular gland (SMG), biochemical and cytochemical studies of adenylate cyclase activity were performed on prenatal and postnatal glands. SMG rudiments and glands were studied from 15 days of gestation op to birth and 1, 2, 3, 4 and 24 weeks after birth. Glands were chemically assayed for adenylate cyclase activity using the procedures of Salomon and coworkers and cytochemically studied using a procedure which was verified biochemically. At 15-16 days of gestation basal adenylate cyclase activity was low and no staining could be observed. Adenylate cyclase activity rose six-fold from the 16th to the 18th day of gestation. Adenylate cyclase staining became evident along the surface of most of the cells of the rudiment at this time. Basal adenylate cyclase activity remained relatively constant from the 18th day of gestation up to 24 weeks of age. However, sequential changes were seen in the cytochemical localization, especially in relation to the apical plasma membrane of the developing secretory cells. (+info)

Facilitation of signal onset and termination by adenylyl cyclase. (6/5304)

The alpha subunit (Gsalpha) of the stimulatory heterotrimeric guanosine triphosphate binding protein (G protein) Gs activates all isoforms of mammalian adenylyl cyclase. Adenylyl cyclase (Type V) and its subdomains, which interact with Gsalpha, promoted inactivation of the G protein by increasing its guanosine triphosphatase (GTPase) activity. Adenylyl cyclase and its subdomains also augmented the receptor-mediated activation of heterotrimeric Gs and thereby facilitated the rapid onset of signaling. These findings demonstrate that adenylyl cyclase functions as a GTPase activating protein (GAP) for the monomeric Gsalpha and enhances the GTP/GDP exchange factor (GEF) activity of receptors. (+info)

The 5'-flanking region of the mouse adenylyl cyclase type VIII gene imparts tissue-specific expression in transgenic mice. (7/5304)

The calcium-stimulated adenylyl cyclases (ACs) play a central role in stimulus-dependent modification of synaptic function. The type VIII AC (AC8) is one of three mammalian calcium-stimulated isoforms, each of which is expressed in a region-specific manner in the CNS. To delineate the DNA sequences responsible for appropriate targeting of AC8 expression, we report here the complete structure of the AC8 gene and define the pattern of expression of the full-length cDNA and its splice variants. In addition to expression within the brain, robust expression of AC8 was also found in the lung. By in situ hybridization, we have found the highest expression of AC8 mRNA within the olfactory bulb, thalamus, habenula, cerebral cortex, and hypothalamic supraoptic and paraventricular nuclei. By generating transgenic mice whose expression of beta-galactosidase is controlled by the AC8 5'-flanking DNA sequences, we demonstrate that the DNA sequences within the 10 kb preceding exon 1 are critical for establishment of this region-specific pattern. This spectrum of sites of production is unique to AC8 among the calcium-stimulated adenylyl cyclases and suggests nonredundant functions with other adenylyl cyclases in neuroendocrine regulation and/or behavior. (+info)

Role of protein kinase A in the maintenance of inflammatory pain. (8/5304)

Although the initiation of inflammatory pain (hyperalgesia) has been demonstrated to require the cAMP second messenger signaling cascade, whether this mechanism and/or other mechanisms underlie the continued maintenance of the induced hyperalgesia is unknown. We report that injection of adenylyl cyclase inhibitors before but not after injection of direct-acting hyperalgesic agents (prostaglandin E2 and purine and serotonin receptor agonists) resulted in reduction in hyperalgesia, evaluated by the Randall-Selitto paw-withdrawal test. In contrast, injection of protein kinase A (PKA) inhibitors either before or after these hyperalgesic agents resulted in reduced hyperalgesia, suggesting that hyperalgesia after its activation was maintained by persistent PKA activity but not by adenylyl cyclase activity. To evaluate further the role of PKA activity in the maintenance of hyperalgesia, we injected the catalytic subunit of PKA (PKACS) that resulted in hyperalgesia similar in magnitude to that induced by the direct-acting hyperalgesic agents but much longer in duration (>48 vs 2 hr). Injection of WIPTIDE (a PKA inhibitor) at 24 hr after PKACS reduced hyperalgesia, suggesting that PKACS hyperalgesia is not independently maintained by steps downstream from PKA. In summary, our results indicate that, once established, inflammatory mediator-induced hyperalgesia is no longer maintained by adenylyl cyclase activity but rather is dependent on ongoing PKA activity. An understanding of the mechanism maintaining hyperalgesia may provide important insight into targets for the treatment of persistent pain. (+info)

"Entrez Gene: ADCY2 adenylyl cyclase 2 (brain)". "Adenylate cyclase type 2". UniProt Consortium. Retrieved 28 May 2014. Stengel ... It belongs to the adenylyl cyclase class-3 or guanylyl cyclase family because it contains two guanylate cyclase domains. ADCY2 ... "Adenylate Cyclase 2 (Brain)". Weizmann Institute of Science. Retrieved 28 May 2014. Xu W, Cohen-Woods S, Chen Q, Noor A, Knight ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (Mar 1999). "Involvement of adenylate cyclase and p70(S6)-kinase ...

https://en.wikipedia.org/wiki/ADCY2

Howlett, A. C.; Fleming, R. M. (1 November 1984). "Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in ...

https://en.wikipedia.org/wiki/Delta-8-Tetrahydrocannabinol

Pituitary adenylate cyclase-activating polypeptide (PACAP)Edit. Pituitary adenylate cyclase-activating polypeptide (PACAP) is ...

https://en.m.wikipedia.org/wiki/Retinohypothalamic_tract

Haga, T; Ross, EM; Anderson, HJ; Gilman, AG (1977). "Adenylate cyclase permanently uncoupled from hormone receptors in a novel ... Haga, T; Haga, K; Gilman, AG (1977). "Hydrodynamic properties of the beta-adrenergic receptor and adenylate cyclase from wild ... Gilman, AG (1984). "G proteins and dual control of adenylate cyclase". Cell. 36 (3): 577-9. doi:10.1016/0092-8674(84)90336-2. ... Sternweis, PC; Northup, JK; Smigel, MD; Gilman, AG (1981). "The regulatory component of adenylate cyclase. Purification and ...

https://en.wikipedia.org/wiki/Alfred_G._Gilman

"Entrez Gene: ADCY3 adenylate cyclase 3". "Gene Cards: ADCY3 Gene". Retrieved 2012-12-30. Human ADCY3 genome location and ADCY3 ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (Mar 1999). "Involvement of adenylate cyclase and p70(S6)-kinase ... Adenylyl cyclase type 3 is an enzyme that in humans is encoded by the ADCY3 gene. This gene encodes adenylyl cyclase 3, which ... Haber N, Stengel D, Defer N, Roeckel N, Mattei MG, Hanoune J (Jul 1994). "Chromosomal mapping of human adenylyl cyclase genes ...

https://en.wikipedia.org/wiki/ADCY3

1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ... "Entrez Gene: ADCY6 adenylate cyclase 6". CS1 maint: discouraged parameter (link) Human ADCY6 genome location and ADCY6 gene ... Adenylyl cyclase type 6 is an enzyme that in humans is encoded by the ADCY6 gene. This gene encodes adenylyl cyclase 6, which ... 1998). "Molecular diversity of adenylyl cyclases in human and rat myometrium. Correlation with global adenylyl cyclase activity ...

https://en.wikipedia.org/wiki/ADCY6

"Entrez Gene: ADCY9 adenylate cyclase 9". Human ADCY9 genome location and ADCY9 gene details page in the UCSC Genome Browser. ... 1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ... Adenylyl cyclase type 9 is an enzyme that in humans is encoded by the ADCY9 gene. Adenylyl cyclase is a membrane bound enzyme ... Cumbay MG, Watts VJ (2004). "Novel regulatory properties of human type 9 adenylate cyclase". J. Pharmacol. Exp. Ther. 310 (1): ...

https://en.wikipedia.org/wiki/ADCY9

"Entrez Gene: ADCY7 adenylate cyclase 7". Human ADCY7 genome location and ADCY7 gene details page in the UCSC Genome Browser. ... 1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ... The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by ... Yan SZ, Tang WJ (2002). "Construction of soluble adenylyl cyclase from human membrane-bound type 7 adenylyl cyclase". G Protein ...

https://en.wikipedia.org/wiki/ADCY7

"Entrez Gene: ADCY5 adenylate cyclase 5". Salim S, Sinnarajah S, Kehrl JH, Dessauer CW (May 2003). "Identification of RGS2 and ... Wang SC, Lai HL, Chiu YT, Ou R, Huang CL, Chern Y (2007). "Regulation of type V adenylate cyclase by Ric8a, a guanine ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (1999). "Involvement of adenylate cyclase and p70(S6)-kinase ... Adenylyl cyclase type 5 is an enzyme that in humans is encoded by the ADCY5 gene. ADCY5 has been shown to interact with RGS2. ...

https://en.wikipedia.org/wiki/ADCY5

"Entrez Gene: ADCY8 adenylate cyclase 8 (brain)". Human ADCY3 genome location and ADCY3 gene details page in the UCSC Genome ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (Mar 1999). "Involvement of adenylate cyclase and p70(S6)-kinase ... Adenylyl cyclase type 8 is an enzyme that in humans is encoded by the ADCY8 gene. Adenylyl cyclase is a membrane bound enzyme ... Parma J, Stengel D, Gannage MH, Poyard M, Barouki R, Hanoune J (Aug 1991). "Sequence of a human brain adenylyl cyclase partial ...

https://en.wikipedia.org/wiki/ADCY8

Brandt DR, Ross EM (January 1985). "GTPase activity of the stimulatory GTP-binding regulatory protein of adenylate cyclase, Gs ... "Purification of the regulatory component of adenylate cyclase". Proceedings of the National Academy of Sciences of the United ... individual subunits of the G protein complex were first identified in 1980 when the regulatory component of adenylate cyclase ... Tang WJ, Gilman AG (December 1991). "Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits". Science. ...

https://en.wikipedia.org/wiki/G_beta-gamma_complex

Another toxin that inhibits the immune response is the adenylate cyclase toxin. This toxin has an intrinsic adenylate cyclase ... The toxin, known as pertussis toxin (or PTx), inhibits G protein coupling that regulates an adenylate cyclase-mediated ... Sebo, Peter; Osicka, Radim; Masin, Jiri (2014-08-04). "Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines". ... Its virulence factors include pertussis toxin, adenylate cyclase toxin, filamentous hæmagglutinin, pertactin, fimbria, and ...

https://en.wikipedia.org/wiki/Bordetella_pertussis

Edema factor is a calmodulin-dependent adenylate cyclase. Adenylate cyclase catalyzes the conversion of ATP into cyclic AMP ( ... The complexation of adenylate cyclase with calmodulin removes calmodulin from stimulating calcium-triggered signaling, thus ...

https://en.wikipedia.org/wiki/Anthrax

... diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. ... Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC1, is a protein that in humans is encoded ... "Entrez Gene: ADCYAP1R1 adenylate cyclase activating polypeptide 1 (pituitary) receptor type I". Ogi K, Miyamoto Y, Masuda Y, ... Miampamba M, Germano PM, Arli S, Wong HH, Scott D, Taché Y, Pisegna JR (May 2002). "Expression of pituitary adenylate cyclase- ...

https://en.wikipedia.org/wiki/ADCYAP1R1

It does so by inhibiting the enzyme adenylate cyclase. The enzyme catalyzes the conversion of adenosine triphosphate (ATP) to 3 ... "Yeast mating pheromone alpha factor inhibits adenylate cyclase". Proceedings of the National Academy of Sciences of the United ... Zhang G, Liu Y, Ruoho AE, Hurley JH (March 1997). "Structure of the adenylyl cyclase catalytic core". Nature. 386 (6622): 247- ...

https://en.wikipedia.org/wiki/Induced_cell_cycle_arrest

August 1984). "Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine ... May DC, Ross EM, Gilman AG, Smigel MD (December 1985). "Reconstitution of catecholamine-stimulated adenylate cyclase activity ... activates hormone-sensitive adenylate cyclase. More than one type of G protein co-exist in the same tissue. For example, in ... The alpha subunit of a stimulatory G protein activated by receptors for stimulatory hormones could stimulate adenylyl cyclase, ...

https://en.wikipedia.org/wiki/Heterotrimeric_G_protein

Guanylyl imidodiphosphate is a potent stimulator of adenylate cyclase. It is often used in studies of protein synthesis. ...

https://en.wikipedia.org/wiki/5'-Guanylyl_imidodiphosphate

Bifunctional hemolysin/adenylate cyclase is a protein that in B. pertussis (the bacteria that causes whooping cough) is encoded ... Carbonetti NH, Artamonova GV, Andreasen C, Bushar N (May 2005). "Pertussis toxin and adenylate cyclase toxin provide a one-two ... This protein in turn is cleaved into a calmodulin-sensitive adenylate cyclase (cyaA-ACD) and hemolysin. Both are virulence ... Ladant D, Ullmann A (April 1999). "Bordatella pertussis adenylate cyclase: a toxin with multiple talents". Trends Microbiol. 7 ...

https://en.wikipedia.org/wiki/CyaA

The cya gene encodes adenylate cyclase, which produces cAMP. In a cya mutant, the absence of cAMP makes the expression of the ... which influences the activity of adenylate cyclase. (In addition, glucose transport also leads to direct inhibition of the ...

https://en.wikipedia.org/wiki/Lac_operon

... activates adenylate cyclase in the absence of ligand. GPR3 is expressed in mammalian oocytes where it maintains meiotic ... 1995). "Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase". Biochem. J ... "Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase". Biochem. J. 309 (Pt ...

https://en.wikipedia.org/wiki/GPR3

One of the most important of the regulated toxins is adenylate cyclase toxin, which aids in the evasion of innate immunity. The ... Fiser R, Masín J, Basler M, Krusek J, Spuláková V, Konopásek I, Sebo P (2007). "Third activity of Bordetella adenylate cyclase ... Gray MC, Donato GM, Jones FR, Kim T, Hewlett EL (2004). "Newly secreted adenylate cyclase toxin is responsible for intoxication ... Hewlett EL, Donato GM, Gray MC (2006). "Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: ...

https://en.wikipedia.org/wiki/Bordetella

Adenylate cyclase is inhibited by agonists of adenylate cyclase inhibitory G (Gi)-protein-coupled receptors. Liver adenylate ... Adenylate cyclase is activated by a range of signaling molecules through the activation of adenylate cyclase stimulatory G (Gs ... This occurs through inhibition of the cAMP-producing enzyme, adenylate cyclase, as a side-effect of glucose transport into the ... cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline. cAMP ...

https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate

... this protein is a stimulatory regulator of adenylate cyclase. Cells containing this mutant form of the Gs protein will continue ...

https://en.wikipedia.org/wiki/Macrodontia_(tooth)

"Entrez Gene: CAP1 CAP, adenylate cyclase-associated protein 1 (yeast)". Hubberstey, A; Yu G; Loewith R; Lakusta C; Young D (Jun ... Adenylyl cyclase-associated protein 1 is an enzyme that in humans is encoded by the CAP1 gene. The protein encoded by this gene ... Yu G, Swiston J, Young D (1994). "Comparison of human CAP and CAP2, homologs of the yeast adenylyl cyclase-associated proteins ... 2004). "Crystal structure of the actin binding domain of the cyclase-associated protein". Biochemistry. 43 (33): 10628-41. doi: ...

https://en.wikipedia.org/wiki/CAP1

... a process regulator related to adenylate cyclase proteins; a profilin with a molecular weight of approximately 14 kDa that is ...

https://en.wikipedia.org/wiki/Actin

H2 receptors are positively coupled to adenylate cyclase via Gs. It is a potent stimulant of cAMP production, which leads to ...

https://en.wikipedia.org/wiki/Histamine_H2_receptor

The M2 and M4 subtypes are Gi/Go-coupled; they decrease intracellular levels of cAMP by inhibiting adenylate cyclase. Their ...

https://en.wikipedia.org/wiki/Acetylcholine

Pituitary adenylate cyclase-activating polypeptide 27 (pro-inflammatory). Eicosanoid receptor Formyl peptide receptor Lipoxin ...

https://en.wikipedia.org/wiki/Formyl_peptide_receptor_2

Epinephrine binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of cyclic AMP ...

https://en.wikipedia.org/wiki/Glycogenesis

"Entrez Gene: CAP2 CAP, adenylate cyclase-associated protein, 2 (yeast)". Human CAP2 genome location and CAP2 gene details page ... Adenylyl cyclase-associated protein 2 is an enzyme that in humans is encoded by the CAP2 gene. This gene was identified by its ... Shibata R, Mori T, Du W, Chuma M, Gotoh M, Shimazu M, Ueda M, Hirohashi S, Sakamoto M (Sep 2006). "Overexpression of cyclase- ... However, the protein appears to be able to interact with adenylyl cyclase-associated protein and actin. CAP2 has been shown to ...

https://en.wikipedia.org/wiki/CAP2

... influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase ...

https://en.m.wikipedia.org/wiki/Photoreceptor_cell