Characterization of muscarinic receptor subtype mediating contraction and relaxation in equine coronary artery in vitro.
In coronary arterial rings isolated from horses, 10(-8)-10(-6) mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with L-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of ACh (10(-14)-10(-8) mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine > or = parafluoro-hexahydrosiladiphenidol (pFHHSiD) > methoctramine. ACh-induced relaxation in the rings with endothelium was inhibited by LNAG or MB, and by each selective antagonist in the following order of potency: 4-DAMP > pFHHSiD > pirenzepine > methoctramine. These results suggest that the ACh-induced contraction and relaxation in equine coronary arteries are mediated mainly by an M3-receptor located on the smooth muscle cells and endothelial cells, respectively, and that the stimulation of the M3-receptor on the endothelial cells liberates nitric oxide.
Obi
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Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Japan.
Kabeyama
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Nishio
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology; D006736:Horses; D066298:In Vitro Techniques; D008751:Methylene Blue; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019335:Nitroarginine; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D019335:Nitroarginine; D001120:Arginine; D000109:Acetylcholine; D008751:Methylene Blue