title: Apamin-sensitive K+ channels involved in the inhibition of acetylcholine-induced contractions in lamb coronary small arteries.
abstract: In vitro experiments were designed to investigate the endothelial factors involved in modulation of the contractile response to acetylcholine in lamb coronary small arteries. Endothelial cell removal, and inhibitors of the L-arginine/nitric oxide (NO) pathway increased basal tension and contractions in response to acetylcholine and abolished relaxations in response to the Ca2+-ionophore, 6S-[6alpha(2S*,3S*),8beta(R*),9beta,11alpha]-5-( methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)et hyl]-1,7-dioxaspiro[5.5]-undec-2-yl]methyl]-4-benzoxazole carboxylic acid (A23187). N(G)-Nitro-L-arginine enhanced acetylcholine-induced contractions in the absence, but not in the presence of the muscarinic M1 receptor antagonist, telenzepine. In contrast to glibenclamide and charybdotoxin, apamin enhanced the acetylcholine-induced contractions and reduced the relaxations caused by A23187 and exogenously added NO. The combination of 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ) and apamin did not further increase the acetylcholine-induced contractions. These results indicate that muscarinic M1 receptor-released endothelial NO inhibits the contractile responses to acetylcholine in lamb coronary small arteries through activation of guanylate cyclase, followed by an increase in apamin-sensitive K+ conductance of the smooth muscle.
authors.affiliation: Departamento de Fisiología, Facultad de Veterinaría, Universidad Complutense de Madrid, Spain.
authors.forename: U
authors.initials: U
authors.lastname: Simonsen
authors.forename: A
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: D
authors.initials: D
authors.lastname: Prieto
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D001120:Arginine / Q000037:antagonists & inhibitors; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D012756:Sheep
chemical_list: D016861:Cyclooxygenase Inhibitors; D007476:Ionophores; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D001030:Apamin; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D000109:Acetylcholine; D002118:Calcium; D007213:Indomethacin