Apamin-sensitive K+ channels involved in the inhibition of acetylcholine-induced contractions in lamb coronary small arteries.
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.
Simonsen
U
U
Departamento de Fisiología, Facultad de Veterinaría, Universidad Complutense de Madrid, Spain.
García-Sacristán
A
A
Prieto
D
D
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
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