Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Taste Buds: Small sensory organs which contain gustatory receptor cells, basal cells, and supporting cells. Taste buds in humans are found in the epithelia of the tongue, palate, and pharynx. They are innervated by the CHORDA TYMPANI NERVE (a branch of the facial nerve) and the GLOSSOPHARYNGEAL NERVE.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Receptors, Adrenergic, alpha: 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.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Rats, Sprague-Dawley: 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.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Sensory Receptor Cells: Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.Binding, Competitive: 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.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Piperidines: A family of hexahydropyridines.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Idazoxan: A benzodioxane-linked imidazole that has alpha-2 adrenoceptor antagonist activity.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Norepinephrine: 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.Receptors, Adrenergic: 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.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Dioxanes: 1,4-Diethylene dioxides. Industrial solvents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), dioxane itself may "reasonably be anticipated to be a carcinogen." (Merck Index, 11th ed)Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Taste: The ability to detect chemicals through gustatory receptors in the mouth, including those on the TONGUE; the PALATE; the PHARYNX; and the EPIGLOTTIS.Propranolol: 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.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Butoxamine: A beta-2 selective adrenergic antagonist. It is used primarily in animal and tissue experiments to characterize BETA-2 ANDRENERGIC RECEPTORS.Adrenergic beta-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Receptors, Adrenergic, beta: 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.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Timolol: A beta-adrenergic antagonist similar in action to PROPRANOLOL. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Cells, Cultured: 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.Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Epinephrine: 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.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Medetomidine: An agonist of RECEPTORS, ADRENERGIC ALPHA-2 that is used in veterinary medicine for its analgesic and sedative properties. It is the racemate of DEXMEDETOMIDINE.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Imidazoles: 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).Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.Doxazosin: A prazosin-related compound that is a selective alpha-1-adrenergic blocker.Isoproterenol: 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.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Signal Transduction: 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.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Guinea Pigs: 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.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Receptors, Cell Surface: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.PyrrolidinesCalcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Calcium: 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.Receptors, Vasopressin: Specific molecular sites or proteins on or in cells to which VASOPRESSINS bind or interact in order to modify the function of the cells. Two types of vasopressin receptor exist, the V1 receptor in the vascular smooth muscle and the V2 receptor in the kidneys. The V1 receptor can be subdivided into V1a and V1b (formerly V3) receptors.Receptor, Endothelin B: A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Structure-Activity Relationship: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.CHO Cells: 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.Kinetics: The rate dynamics in chemical or physical systems.Olfactory Receptor Neurons: Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN.Rats, Inbred Strains: 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.2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.Chorda Tympani Nerve: A branch of the facial (7th cranial) nerve which passes through the middle ear and continues through the petrotympanic fissure. The chorda tympani nerve carries taste sensation from the anterior two-thirds of the tongue and conveys parasympathetic efferents to the salivary glands.Olfactory Mucosa: That portion of the nasal mucosa containing the sensory nerve endings for SMELL, located at the dome of each NASAL CAVITY. The yellow-brownish olfactory epithelium consists of OLFACTORY RECEPTOR NEURONS; brush cells; STEM CELLS; and the associated olfactory glands.Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)Oligopeptides: Peptides composed of between two and twelve amino acids.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Molecular Sequence Data: 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.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Tubocurarine: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Spiro Compounds: A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Protein Binding: 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.Mice, Inbred C57BLSialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Serotonin 5-HT1 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.Sulfonamides: A group of compounds that contain the structure SO2NH2.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.Patch-Clamp Techniques: 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.QuinoxalinesPiperazinesElectric Stimulation: Use of electric potential or currents to elicit biological responses.Amino Acid Sequence: 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.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.BenzodiazepinonesBiphenyl CompoundsReceptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers.Behavior, Animal: The observable response an animal makes to any situation.Benzazepines: Compounds with BENZENE fused to AZEPINES.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Gallamine Triethiodide: A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)RNA, Messenger: 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.Cyclic AMP: 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.Brain: 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.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Alcuronium: A non-depolarizing skeletal muscle relaxant similar to TUBOCURARINE. It is used as an anesthesia adjuvant.TetrazolesReceptors, Tachykinin: Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.Receptors, Opioid: 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.Chemoreceptor Cells: Cells specialized to detect chemical substances and relay that information centrally in the nervous system. Chemoreceptor cells may monitor external stimuli, as in TASTE and OLFACTION, or internal stimuli, such as the concentrations of OXYGEN and CARBON DIOXIDE in the blood.Xanthines: Purine bases found in body tissues and fluids and in some plants.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Tongue: A muscular organ in the mouth that is covered with pink tissue called mucosa, tiny bumps called papillae, and thousands of taste buds. The tongue is anchored to the mouth and is vital for chewing, swallowing, and for speech.Serotonin Receptor Agonists: Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.Adenosine: 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.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.Indoles: 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.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Vomiting: The forcible expulsion of the contents of the STOMACH through the MOUTH.PyridazinesPyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Receptors, Muscarinic: 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.Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.Rabbits: 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.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Receptors, Drug: 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.Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Strychnine: An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Antihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.Bicyclo Compounds, Heterocyclic: A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Stimulation, Chemical: 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.Purinergic P2X Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.Azepines: Seven membered heterocyclic rings containing a NITROGEN atom.Necturus: A genus of the Proteidae family with five recognized species, which inhabit the Atlantic and Gulf drainages.Dihydro-beta-Erythroidine: Dihydro analog of beta-erythroidine, which is isolated from the seeds and other plant parts of Erythrina sp. Leguminosae. It is an alkaloid with curarimimetic properties.Membrane Potentials: 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).Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.Receptors, Neurokinin-1: A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Pirenzepine: An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.Purinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Necturus maculosus: A neotenic aquatic species of mudpuppy (Necturus) occurring from Manitoba to Louisiana and Texas.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Isothiuronium: An undecenyl THIOUREA which may have topical anti-inflammatory activity.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Tetrahydronaphthalenes: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.Receptors, Purinergic P2Y1: A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM.Drug Antagonism: Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Receptors, Glycine: Cell surface receptors that bind GLYCINE with high affinity and trigger intracellular changes which influence the behavior of cells. Glycine receptors in the CENTRAL NERVOUS SYSTEM have an intrinsic chloride channel and are usually inhibitory.Receptors, Cholecystokinin: Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.Receptors, Purinergic: 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.Vas Deferens: The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.Cannabinoid Receptor Antagonists: Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.
  • For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by alpha-adrenergic receptor activation. (wikipedia.org)
  • It has been established in dog experiments that histamine (0.05 mg/kg) induces a considerable rise in blood coagulation, an increase in prothrombin consumption and plasma tolerance to heparin a diminution of fibrinase content and enhancement of fibrinolysis. (saladgaffe.ml)
  • A unique feature of this drug is that it does not promote the anxiety symptoms, sexual symptoms, or insomnia, which are commonly associated with SSRI and SNRI therapy.20 Mesyrel acts on various receptors, including certain histamine, serotonin, and adrenergic receptors, distinguishing it from other antidepressants that cover a narrow range of neurotransmitters. (storysteel.ml)
  • While a number of these loci harbor gene targets of currently approved therapies, such as statins and PCSK9 inhibitors, the majority of the annotated genes at these loci encode for proteins involved in vessel wall function with no known drugs available. (frontiersin.org)
  • We essentially focused on our recent studies in which we addressed the concept of preassembly vs. the agonist-dependent interaction between the protease-activated receptor 1 (PAR1) and its cognate G proteins. (frontiersin.org)
  • Any of a large number of proteins that are produced normally by specialized cells after stimulation by an antigen (e.g., a bacterium, virus, parasite, etc.) and act specifically against the antigen in an immune response. (cdc.gov)
  • Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. (hindawi.com)
  • These destructive effects result in damage to the production capacity of energy, proteins and enzymes and lead to the accumulation of undesirable biological material into cells. (biocellmedical.com)
  • Large molecules are incorporated by endocytosis and the smaller molecules are incorporated by simple diffusion or diffusion provided by receptor proteins, as appropriate. (biocellmedical.com)
  • CysLT 1 and CysLT 2 receptors can couple to distinct types of G proteins. (biologists.org)
  • They are the proteins that regulate almost all cell processes from cell division in cancer to neuronal signal transduction in learning and memory. (ox.ac.uk)
  • The dopamine D 1 receptor belongs to the superfamily of heptahelical receptors that modulate the activity of effectors such as adenylate cyclase by activation of specific heterotrimeric GTP-binding proteins (G proteins). (aspetjournals.org)
  • The coupling of the receptor to heterotrimeric G proteins is inhibited by the binding of β-arrestin, which is likely to be the immediate cause of rapid desensitization. (aspetjournals.org)
  • The endoplasmic reticulum (ER) of eukaryotic cells is involved in the synthesis and processing of proteins and lipids in the secretory pathway. (statescale.cf)
  • Antibodies valuable in search labeling ocular tissues are the even so ones applied in other organs with blockage of antibodies against cell molecules together to the fondness as photoreceptor opsins (Anti-Opsin red, sward, and unhappy and anti-rhodopsin) and against RPE cell proteins (anti-RPE65). (kavalerist.ru)
  • Recently, new evidence has accumulated showing the existence of several novel receptor interacting proteins and various angiotensin II receptor activation mechanisms beyond the classical actions of receptors for Ang II. (ahajournals.org)
  • These associated proteins could contribute not only to Ang II receptors' functions, but also to influencing pathophysiological states. (ahajournals.org)
  • Here, we have summarized these emerging concepts concerning Ang II receptor interacting proteins and discuss new potent therapeutic targets in cardiovascular disease. (ahajournals.org)
  • p38/Tie2 kinase inhibitor Arry-614 binds to and inhibits the activities of p38 and Tie2 kinases, which may inhibit the production of proinflammatory cytokines and may decrease tumor angiogenesis and tumor cell growth and survival. (unt.edu)
  • Here, we demonstrate that PLC-gamma 1 acts as a guanine nucleotide exchange factor (GEF) for PIKE (phosphatidylinositol-3-OH kinase (PI(3)K) enhancer). (jove.com)
  • A organized S10-1 additional apparatus made systemic substance of a acknowledged kinase of available Crataegus strokes( Crataegisan) in the transplantation of symptoms with COPD Source atrium NYHA II. (seabaygame.com)
  • Importantly many of the associated genes linked to vascular (smooth muscle, endothelial, and macrophage) cell processes are now organized into distinct functional pathways, e.g., vasodilation, growth factor responses, extracellular matrix and plaque remodeling, and inflammation. (frontiersin.org)
  • The extracellular part of the receptor can be glycosylated. (cusabio.com)
  • Two highly conserved cysteine residues of the extracellular loop can form disulfide bonds to stabilize the receptor structure. (cusabio.com)
  • This is not a fixed structure but its function depends on the complex interplay between the different cell types such as the endothelial cells, astrocytes, pericytes, and the extracellular matrix of the brain and blood flow maintained in the microvessels or brain capillaries. (hindawi.com)
  • Activation of the PBAN receptor (PBANR) triggers a signal transduction cascade that utilizes an influx of extracellular Ca 2+ to drive the concerted action of multiple enzymatic steps (i.e. chain-shortening, desaturation, and fatty acyl reduction) that generate the multicomponent pheromone blends specific to each species. (springer.com)
  • Mutation of a conserved Asp (D98) in the rat serotonin (5HT) transporter (rSERT) to Glu (D98E) led to decreased 5HT transport capacity, diminished coupling to extracellular Na + and Cl − , and a selective loss of antagonist potencies (cocaine, imipramine, and citalopram but not paroxetine or mazindol) with no change in 5HT K m value. (jneurosci.org)
  • The potency of an antagonist is usually defined by its half maximal inhibitory concentration (i.e. (wikipedia.org)
  • The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. (ox.ac.uk)
  • In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). (ox.ac.uk)
  • The inhibitory effects of carvedilol, M14 or M21 on ET-1 production were not reversed by N Nitro-L-arginine methyl ester (L-NAME) (1.9 mM), or by indomethacin (1.5 microM), suggesting that mechanisms other than the stimulation of nitric oxide or prostacyclin production were involved. (termsreign.ga)
  • The hate of antibodies to block T-cell inhibitory receptors such as CTLA-4 and PD-1 can initiate to level activation and proliferation of tumor-specific T cells, preventing anergy or tiredness and thereby allowing the improvement of an effec- tive tumor-specific unsusceptible response. (kavalerist.ru)
  • Traditional acupuncture-induced antinociception is considered to be mediated by activation of the descending pain inhibitory system (DPIS) including initiation of its opioidergic, adrenergic and serotonergic components. (apitoxina.cl)
  • Although up to 24-hr exposure to 100 ng/ml pertussis toxin did not alter resting mast cell cyclic AMP levels, the ability of adenosine to elevate cell cyclic AMP concentrations was diminished markedly by doses of the toxin higher than those required to affect mediator release. (saladgaffe.ml)
  • To summarize, reflecting preferential blockade of D 3 versus D 2 receptors, S33138 preserves and/or enhances cognitive function, increases frontocortical cholinergic transmission, and is active in models of antipsychotic properties at doses well below those inducing catalepsy. (aspetjournals.org)
  • Such impact allows persons to take lower doses than would be necessary with either drug alone, thereby minimizing any undesired actions of the drugs. (kiwiandanemu.org)
  • the very large doses formerly used un-doubtedly induced dangerous cheap soma 500mg in the uk online symptoms occasionally, but there islittle risk of this occurring from the intelligent use of the less violentmembers of the series. (synapsys.me)
  • Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at doses much greater than required for beta blockade. (nih.gov)
  • Equivalent maximal beta-blocking effect is achieved with oral and intravenous doses in the ratio of approximately 2.5:1. (nih.gov)
  • Some of the atypical antipsychotics like lurasidone and aripiprazole are also partial agonists at the 5-HT 1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs). (wikidoc.org)
  • Flesinoxan at doses of Adrenergic Receptors thirty and one hundred )u. g/kg s. c. enhanced heart rate and respiratory rate but lowered systolic and diastolic blood stress. (fxr-agonists.com)
  • We examined the interrelationships of internalization and down-regulation of the β 2 -adrenergic receptor in response to treatment of the BEAS-2B human epithelial cell line with both a series of agonists at high occupancy and with various concentrations of fenoterol that gave occupancies from 0.93 to 0.001. (aspetjournals.org)
  • Good proportionality was observed between the strength of an agonist (coupling efficiency) and its capacity at high occupancy to induce the rapid phase of desensitization, internalization, and phosphorylation. (aspetjournals.org)
  • In this study, we have examined the effect of coupling efficiency on down-regulation of the β 2 -adrenergic receptor (β-AR) and the relationship between the extent of internalization and down-regulation. (aspetjournals.org)
  • It has been suggested ( Koenig and Edwardson, 1997 ) that the extent of down-regulation may be proportional to the level of internalized receptor and that down-regulation may proceed at a rate independent of the level of internalization, indicating that it does not saturate. (aspetjournals.org)
  • In this study we examined the role of JNK in regulating opioid receptor signaling and found that activation of the JNK pathway is required for acute tolerance to morphine and related opioids, but not fentanyl or other agonists that efficiently activate GRK/β-arrestin-dependent internalization. (pnas.org)
  • Apart from oxytocin, other molecules such as arginine vasopressin (AVP) and oxytocin agonists or antagonists are able, because of their similar structure, to bind to the receptor. (hindawi.com)
  • The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP), which uses a weight‐of‐evidence analysis based on data from several assays to identify the potential for chemicals to act as agonists or antagonists of the estrogen or androgen receptors (ER, AR), or inhibitors of steriodogenic enzymes. (environmental-expert.com)
  • Benign prostatic hyperplasia (BPH) and overactive bladder syndrome (OAB), which are representative diseases of voiding dysfunction, are the main targets of these drugs, and tremendous efforts are underway to develop more potent and beneficial drugs for these diseases. (einj.org)
  • Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. (kiwiandanemu.org)
  • Met Val Gln Glyor a 10- to 109-amino fibrinogen process hypertrophied as the open congestive aquaporin-2 for pure, upright or fluid BNP in stage The acids of the threshold can have issued into ischemic concentrations and called to form people used with systemic pancreatobiliary human cells, chronically potent disease gland. (seabaygame.com)
  • Effect of testosterone suppression on the pharmacokinetics of a potent gnRH receptor antagonist. (pharmacogenomicsguide.com)
  • Regarding the properties of P-gp on membrane capacity depolarization, the coadministration of drugs designed to keep off transporter over-expression or specific inhibitors of transporters work could pre- vent refractoriness and/or epileptogenesis, as suggested above. (edelstar-shop.ru)
  • In relation to voiding symptoms, approximately seven groups of drugs are used clinically, such as alpha-adrenoceptor antagonists, 5-alpha reductase inhibitors, antimuscarinics, phosphodiesterase type 5 (PDE5) inhibitors, beta-agonists, botulinum toxin (botox), and phytotherapic supplements [ 1 ]. (einj.org)
  • At present, the main drugs for treatment of BPH are alpha-adrenergic antagonists and 5-alpha-reductase inhibitors, but new drugs with different underlying mechanisms are in development [ 3 ]. (einj.org)
  • Antimuscarinic agents are still the most representative drugs for OAB, but recent treatments for OAB have shown great changes, such as the emergence of new acting types of drugs, including beta-3 adrenergic agonists, PDE5 inhibitors, and botox. (einj.org)
  • important irritability acid will be investigated bloating message to happen Ca2+-responsiveness of ST. We underlie that belonging mammals to mental generation will fall in a jugular cell to cardiac failure as low consumption typically returning that undergoing sleep inhibitors may diagnose renal for tachyarrythmias with CHF. (siriuspixels.com)
  • Statins are a class of medications that are competitive inhibitors of Hydroxy Methyl Glutaryl Co-enzyme A (HMG-CoA) reductase which is the rate-limiting enzyme in the cholesterol bio-synthesis pathway. (statescale.cf)
  • In this study, patients treated with Metoprolol received the drug both very early intravenously and during a subsequent 3 month period, while placebo patients received no beta-blocker treatment for this period. (zura.info)
  • The study thus was able to show a benefit from the overall Metoprolol regimen but cannot separate the benefit of very early intravenous treatment from the benefit of later beta-blocker therapy. (zura.info)
  • Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol. (zura.info)
  • Metoprolol tartrate USP, is a selective beta 1 -adrenoreceptor blocking agent, available in 5-mL vials for intravenous administration. (nih.gov)
  • Metoprolol is a beta 1 -selective (cardioselective) adrenergic receptor blocker. (nih.gov)
  • This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta 2 -adrenoreceptors, chiefly located in the bronchial and vascular musculature. (nih.gov)
  • By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris. (nih.gov)
  • Relative beta 1 selectivity is demonstrated by the following: (1) in healthy subjects, metoprolol is unable to reverse the beta 2 -mediated vasodilating effects of epinephrine. (nih.gov)
  • Metoprolol tartrate is a selective beta 1 -adrenoreceptor blocking agent, available as 25 mg, 50 mg, and 100 mg tablets for oral administration. (drugs.com)
  • Metoprolol tartrate is (±)-1-(isopropylamino)-3-[ p -2-methoxyethyl)phenoxy]-2-propanol (2:1) dextro -tartrate salt. (drugs.com)
  • 1. Metoprolol CX/XL, which was studied in the Metoprolol CR/XL (Controlled Release/Extended Release) Randomized Intervention Trial in Chronic Heart Failure. (clinicaladvisor.com)
  • The sustained delivery of beta blockade may account for the superior benefit of extended release metoprolol. (clinicaladvisor.com)
  • Radiation induces acute alterations in neuronal function. (ox.ac.uk)
  • Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. (ox.ac.uk)
  • These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study. (ox.ac.uk)
  • Significance epilepticus induces time-dependent neuronal and astrocytic expres- sion of interleukin-1 receptor prototype I in the rat limbic system. (play-uno.ru)
  • Since neuronal VIP mise en scene was not affected in the bone-marrow chimeras, the increased anti-viral reply was attributed to the require of VIP performance at hand hematopoietic cells (Li et al. (kramskoy.info)
  • A 19 amino acid peptide, rho-TIA, has been reported to produce non-competitive blockade of α 1B -adrenoceptor mediated inositol phosphate formation at concentrations having little effect on this response in cells expressing the other α 1 subtypes. (guidetopharmacology.org)
  • These per se melanin dispersal effects were also found to be markedly potentiated by isoprenaline, which is a specific beta-adrenoceptor agonist. (worldwidescience.org)
  • A chemical substance (such as a drug) that is capable of combining with a receptor on a cell and initiating the same reaction or activity typically produced by the binding of a substance that normally occurs in the body (i.e., is endogenous). (cdc.gov)
  • They are in effect weak agonists that stimulate the beta receptors to a lesser degree than endogenous catecholamines. (clinicaladvisor.com)
  • Amrinones net hemodynamic effects are similar to those of dobutamine, however, because the drug does not stimulate beta adrenergic receptors, it may be effective in patients with CHF who do not respond to dobutamine or other inotropic agents. (powershow.com)
  • Pro-inflammatory cytokines such as IL-1 and IL-6 stimulate the development of CRH and thus may be driving this dysregulation (Maes et al. (casaelviejocactus.com)
  • Increasing the plasma level of insulin by administration of sulfonylureas (e.g. tolbutamide and glipizide) or meglitinide, which stimulate the pancreatic (3-cells to secrete more insulin, and/or by injection of insulin when sulfonylureas or meglitinide become ineffective, can result in insulin concentrations high enough to stimulate the very insulin-resistant tissues. (allindianpatents.com)
  • Rodent studies also cater salutary perspicaciousness into the density organs that are most vulnerable to the carcinogenicity of a postulated compound while also clarifying the types of tumours that can occur: compounds that draw out kind tumours stimulate less worry than agents that induce virulent neoplasias. (kavalerist.ru)
  • Angiotensin II (Ang II) is the principal vasoactive substance of the renin-angiotensin system (RAS), having a variety of physiological actions including vasoconstriction, aldosterone release, and cell growth. (ahajournals.org)
  • Curr Protoc Chem Biol, 4: Cabazitaxel exerts its effects by inhibiting microtubule growth and assembly, processes that are essential for cells to divide. (wordcycler.com)
  • Angiotensin (Ang) II exerts its important physiological functions through 2 distinct receptor subtypes, type 1 (AT 1 ) and type 2 (AT 2 ) receptors. (ahajournals.org)
  • Restoring the resting potential brings maturity to induced stem cell-derived human cardiac myocytes. (stanford.edu)
  • Aminophylline competitively antagonizes the cardiac actions of adenosine at the cell surface receptors. (wikipedia.org)
  • During the initial upstroke of action potential in a normal cardiac cell, a rapid net influx of positive ions (Na + and Ca ++ ) occurs, which results in the depolarization of the cell membrane. (medscape.com)
  • Antiarrhythmic drugs play a central role in the treatment of cardiac arrhythmias in childhood. (thoracickey.com)
  • In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. (rxlist.com)
  • This hurts an significant satellite to drag an weight base velocity that could quell considered for an cardiac technique or human travel aspects. (favorlabel.com)
  • This is molecules that are muscular cohorts, active failure, myocardial person, overall blood and Abstract, IL-1 and cardiac system, and congestive P, the capable form of this discharge will produce having compounds on all substituted ergometers. (siriuspixels.com)
  • With a dedicated cardiac camera, these images can be obtained over 10 min with an effective radiation dose of less than 1 mSv without significant sacrifice of accuracy. (termsreign.ga)
  • Although the exercise of most regulatory systems is linked over the congestive 10 to 20 cells, the Skeleton and beta of electric membrum myocardium is hospitalized at a cardiac Pathophysiology. (hone.world)
  • This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients. (hindawi.com)
  • A fusion DNA vaccine containing the first domain of fragment C (FrC) of tetanus toxin (TT865-1120) (p.DOM) fused to the human Wilms' Tumor gene-1 (WT1)-derived MHC class I-binding epitope WT1.126, with potential antitumor activity. (unt.edu)
  • 75 Intestinal carcinoid tumor: A yellow, well-differentiated, circumscribed tumor that arises from enterochromaffin cells in the small intestine or, less frequently, in other parts of the gastrointestinal tract. (malacards.org)
  • Cytotoxic T-cells (Tc), which are CD8+, engage in battle and destroy virally infected cells as graciously as tumor cells. (kramskoy.info)
  • As mentioned earlier, since ovarian cancers, the more than half of which are high-grade serous adenocarcinomas, genetic insta- bility in tumor cells has been linked with opposition to cyto- toxic and other tumor cell-directed therapies. (kavalerist.ru)
  • In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. (hindawi.com)
  • A single nucleotide polymorphism (SNP) in exon 1 of the μ-opioid receptor gene ( OPRM1 ), in which an adenine-to-guanine substitution (A118G) exchanges an asparagine for an aspartic acid at a putative N-glycosylation site (N40D), is common in persons of European (15−30%) and Asian ancestry (49-60%), with lower prevalence in African American and Hispanic populations ( 1 - 3 ). (pnas.org)
  • The prevalence of exercise-induced bronchoconstriction is reported to be high among recreational and elite athletes, yet diagnosis is often symptom-based. (bactrim2020.site)
  • http://symatlas.gnf.org ), and conserved chromosomal synteny ( http://genome.ucsc.edu/cgi-bin/hgTracks ), we generated the mouse equivalent of the human SNP rather than replacing the mouse Oprm1 gene with the human OPRM1 gene in exon 1. (pnas.org)
  • however, gene knockout of JNK 1 selectively blocked κ-receptor inactivation, whereas deletion of JNK 2 selectively blocked MOR inactivation. (pnas.org)
  • A novel species of replicative-form (RF) DNA was found in cells infected with a phage mutant of gene B, C, D, F, or G. Observations on the hematic diffusion of spiramycin following administration by rectal route We screened plasma samples for HSV-2 infection from 826 women aged 15-34 years who participated in an HIV-1 survey in Kilifi in 2004. (termsreign.ga)
  • Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms. (pharmacogenomicsguide.com)
  • The serotonin 1A receptor is encoded by the HTR1A gene . (wikidoc.org)
  • Tumours therefore have significantly enhanced [ 18 F]FDG uptake compared with normal cells, so [ 18 F]FDG PET is routinely used in diagnosing and monitoring cancers. (openmedscience.com)
  • Since these mediators accumulate at sites of inflammation, and inflammatory cells express both classes of receptors, their responses are likely to be crossregulated. (biologists.org)
  • By analogy to the other antipsychotics, S33138 (0.63-10.0 mg/kg s.c.) inhibited conditioned avoidance responses in rats, apomorphine-induced climbing in mice, and hyperlocomotion elicited by amphetamine, cocaine, dizocilpine, ketamine, and phencyclidine in rats. (aspetjournals.org)
  • Alongside these discoveries, as toxicologists used molecular tools to probe cubicle responses to electrophiles, they learnt that cells are not fully unguarded against these damaging species. (kavalerist.ru)
  • Thus, the difference in the prolactin responses to systemic administration of the drugs may not only be due to a difference in the distribution of kainate and NMDA receptors but also to the steady state level of activity of the prolactin-releasing and -inhibiting factors which is determined by the reproductive state of the animal. (storysteel.ml)
  • In the present study, behavioral and in vivo electrophysiological methods were used to examine the peripheral effects of propofol on tonic ongoing pain-related responses produced by subcutaneous bee venom-induced inflammatory pain state. (apitoxina.cl)
  • It involves numerous cell types (smooth muscle cells, endothelial cells, and macrophages) and often manifests in myocardial infarction. (frontiersin.org)
  • Blood brain barrier (BBB) is a vasculature of the central nervous system (CNS) that is formed by capillary endothelial cells. (hindawi.com)
  • BBB is physically located in endothelium of blood vessels (capillaries) and acts as a "physical barrier" due to formation of complex tight junctions between adjacent endothelial cells. (hindawi.com)
  • Thus, association of astrocytes with the brain endothelial cells provides a modular organization that allows precise control over the substances that enter or leave the brain. (hindawi.com)
  • It includes endothelial cells, astrocytes, and blood capillaries in the brain, which form the major structural component of the blood brain barrier. (hindawi.com)
  • These are quite different from other capillaries found in the body as their endothelial wall possesses tight junctions which obstruct transport between cells. (hindawi.com)
  • More specifically, the endothelial cells also possess transporters which show permeability characteristics and allow transport of oxygen and CO 2 across the BBB, bu these selectively prevent other substances from crossing [ 1 ]. (hindawi.com)
  • Tie2 is an endothelial cell specific receptor that is activated by angiopoietins, growth factors required for angiogenesis. (unt.edu)
  • This agent has also been reported to inhibit other kinases including vascular endothelial growth factor receptor (VEGFR2) and Src tyrosine kinases. (unt.edu)
  • Epinephrine or phenylephrine neither increased the basal release of PGI2 from bovine aortic endothelial cells nor potentiated the stimulatory action of adenine nucleotides, which is mediated by P2-purine receptors. (tabsforsale24h.bid)
  • While studies have shown that miRs can regulate the activity and interplay of vascular inflammatory cells, endothelial cells, smooth muscle cells and fibroblasts, all key elements leading to AAA formation, much work remains to be done. (stanford.edu)
  • The A118G SNP has been associated with an altered vulnerability to opioid addiction ( 4 - 6 ), a decreased response to opioid-induced analgesia ( 7 , 8 ), and an enhanced response to therapies for alcohol ( 9 , 10 ) and nicotine addiction ( 7 , 11 ). (pnas.org)
  • In the postoperative setting where opioids are widely used, nausea and vomiting delay recuperation and hospital discharge, as can opioid-induced constipation, especially in cases of postoperative ileus ( Marderstein and Delaney, 2008 ). (aspetjournals.org)
  • Thus, the effects of prenatal ethanol exposure on the total expression of NR1 splice variants and the cell surface expression of both NR1 and NR2 subunits in brain were investigated in rats. (ox.ac.uk)
  • Kindling in rats was slowed as sumptuously: 1 h of VNS former to the kindling pulsation increased the average swarm of stimuli needed to reach the generalized commandeering state (Naritoku and Mikels 1997). (casaelviejocactus.com)
  • Protection by Nigella sativa against carbon tetrachloride-induced downregulation of hepatic cytochrome P450 isozymes in rats. (pharmacogenomicsguide.com)
  • Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). (bvsalud.org)
  • We will readmission these antioxidants to write collagenolysis Melanocytes in candidate antibodies transoesophageal to the beta major concerning cells( the pump for ANP, BNP, the Oliguria A and C spinal likelihood women, and percent). (augenta.net)
  • Transfection of cDNAs encoding either the 1.7- or the 1.3-kilobase T11 mRNA into COS-1 cells resulted in expression of surface T11 epitopes as well as sheep-erythrocyte-binding capacity. (statescale.tk)
  • The results showed that ingestion of PAH-contaminated mussels induced CYP1A1 mRNA and EROD activity. (saladgaffe.cf)
  • These changes in repolarization do not occur in all myocardial cells. (medscape.com)
  • There are numerous studies in adults showing that class I antiarrhythmic drugs do not reduce mortality, but even increase it in patients with ventricular tachycardia and myocardial ischemia. (thoracickey.com)
  • We will n't indicate the failure of these disorders with congestive training, myocardial MRIdetermined LVH, and viable alpha-1-adrenergic muscle in the two such journals. (augenta.net)
  • For local use of these drugs should be halted until hemodynamic changes occur, including oxygen saturation, end-tidal co2 concentration. (yogachicago.com)
  • hemodynamic and transitional Cell phenomena of atrial Internet on analogs, preferences, and peripheral Nitrovasodilators in agents with many patient hypertrophy. (seabaygame.com)
  • 9. The composition of claim 1, wherein said immunoglobulins exhibit increased antibody-dependent cellular cytotoxicity (ADCC) activity. (freepatentsonline.com)
  • Randomized phase II trial of letrozole plus anti-MUC1 antibody AS1402 in hormone receptor-positive locally advanced or metastatic breast cancer. (pharmacogenomicsguide.com)
  • This Cell Signaling Technology antibody is immobilized via covalent binding of primary amino groups to N-hydroxysuccinimide (NHS)-activated Sepharose® beads. (cellsignal.com)
  • This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in human cells. (cellsignal.com)
  • An abnormal deficiency in the oxygen-carrying component of the blood, measured in unit volume concentrations of hemoglobin, red blood cell volume, or red blood cell number. (cdc.gov)
  • pulse: multivariate term identified to any resistance, energy, order or inspiratory beta which is or transfers Hemodialysis of concentrations or continuous patients. (adams-farm.com)
  • Concentrations of serum cortisol, progesterone, estradiol-17 beta, cholesterol and cholesterol ester in the doe during the reproductive stadium, in the fetal serum, in the amniotic fluid and in the milk of rabbits, as well as correlations between these parameters. (saladgaffe.ml)
  • Elasmobranchs detect small potentials using excitable cells of the ampulla of Lorenzini which have calcium-activated K(+) channels, first described in 1974. (stanford.edu)
  • Consequently, thimerosal may induce or inhibit cellular functions dependent on calcium signaling. (medindex.am)
  • A DNA construct is an artificially constructed segment of nucleic acid that is going to be "transplanted" into a target tissue or cell. (keywen.com)
  • You can identify a time tissue and evaluate your cells. (adams-farm.com)
  • In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. (ox.ac.uk)
  • Fluoroptic thermometry was used to record temperatures on the tissue surface and at depths of 1 mm and 2 mm during continuous delivery of RF energy at 1, 2, 3, 4, 5, and 10 second time increments. (bactrim2020.site)
  • GLUT1 has widespread expression and catalyses the energy-independent facilitated diffusion of glucose down its concentration gradient across red blood cell membranes, blood-brain and blood-tissue barriers and membranes of some oragnelles. (openmedscience.com)
  • Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within one hour after oral administration, and its duration is dose related. (drugs.com)