Presynaptic M2-muscarinic receptors on noradrenergic nerve endings and endothelium-derived M3 receptors in cat cerebral arteries. 1991

M J Alonso, and S Arribas, and J Marín, and G Balfagón, and M Salaices
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.

The muscarinic (M) receptors involved in the vasodilation elicited by acetylcholine (ACh) and in the carbachol inhibition in electrically induced [3H]noradrenaline (NA) release in cat cerebral arteries was investigated. For this, atropine, pirenzepine, AF-DX 116, 4-DAMP, non-specific, M1, M2 and M3 receptor antagonists, respectively, were used. ACh elicited concentration-dependent relaxations up to 10(-6) M which were attenuated by these antagonists; the order of potency (pA2 values) to inhibit the ACh-induced relaxation was: atropine (10.1) 4-DAMP (8.9) greater than pirenzepine (7.6) greater than AF-DX 116 (5.9). The electrical stimulation (200 mA, 0.3 ms, 2 Hz, during 1 min) of these arteries preincubated with [3H]NA caused tritium release which was inhibited by carbachol (10(-6) M). The 4 antagonists attenuated the action of the M agonist; the order of potency (pIC50 values) was: atropine (8.7) greater than 4-DAMP (8.1) greater than AF-DX 116 (7.9) greater than pirenzepine (5.8). The action of McN-A-343, a putative M1 agonist, was also investigated. This agent produced small vasodilator responses and elevated concentrations (5 x 10(-5) M) inhibited the stimulated NA release, which was partially antagonized by atropine (10(-7) M) and pirenzepine (10(-8) and 10(-7) M). These results suggest the existence of M3 and M2 receptors mediating the relaxation induced by ACh and the NA release inhibition evoked by carbachol, respectively.

UI MeSH Term Description Entries
D008297 Male Males
D008455 (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride A drug that selectively activates certain subclasses of muscarinic receptors and also activates postganglionic nicotinic receptors. It is commonly used experimentally to distinguish muscarinic receptor subtypes. McN A-343,McN-A-343,McN-A343,McNeil A 343,A 343, McNeil,McN A 343,McN A343,McNA343
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009638 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 that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010276 Parasympatholytics Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. Antispasmodic,Antispasmodic Agent,Antispasmodic Drug,Antispasmodics,Parasympathetic-Blocking Agent,Parasympathetic-Blocking Agents,Parasympatholytic,Parasympatholytic Agent,Parasympatholytic Drug,Spasmolytic,Spasmolytics,Antispasmodic Agents,Antispasmodic Drugs,Antispasmodic Effect,Antispasmodic Effects,Parasympatholytic Agents,Parasympatholytic Drugs,Parasympatholytic Effect,Parasympatholytic Effects,Agent, Antispasmodic,Agent, Parasympathetic-Blocking,Agent, Parasympatholytic,Agents, Antispasmodic,Agents, Parasympathetic-Blocking,Agents, Parasympatholytic,Drug, Antispasmodic,Drug, Parasympatholytic,Drugs, Antispasmodic,Drugs, Parasympatholytic,Effect, Antispasmodic,Effect, Parasympatholytic,Effects, Antispasmodic,Effects, Parasympatholytic,Parasympathetic Blocking Agent,Parasympathetic Blocking Agents
D010277 Parasympathomimetics Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here. Parasympathomimetic Agents,Parasympathomimetic Drugs,Parasympathomimetic Effect,Parasympathomimetic Effects,Agents, Parasympathomimetic,Drugs, Parasympathomimetic,Effect, Parasympathomimetic,Effects, Parasympathomimetic
D010880 Piperidines A family of hexahydropyridines.
D010890 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. Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D011976 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. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto

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