Concentration-dependent desensitization of isolated porcine coronary arterial segments to acetylcholine.
Acetylcholine elicited an increase in developed tension on isolated porcine coronary arterial rings at concentrations exceeding 1.1 x 10(-7) M. However, at concentrations greater than 3.3 x 10(-6) M, desensitization occurred with repeated exposures to acetylcholine. When rings were first exposed to 3.3 x 10(-6) M, then washed and subsequently exposed to 3.3 x 10(-5) M, tension was either unchanged or significantly reduced, giving rise to two different population effects. Although atropine completely antagonized the effect of acetylcholine, pretreatment with methysergide (5-HT2), mepyramine (H1) and prazosin (alpha 1) did not attenuate acetylcholine-induced desensitization, indicating that the phenomenon is unrelated to either serotonin, H1- or alpha-adrenergic receptor activation. Diltiazem and nifedipine significantly reduced or completely inhibited contractions produced by K+ depolarization, but not those produced by acetylcholine. Moreover, ryanodine did not alter the tension developed by repeated exposures to acetylcholine. Our results suggest that acetylcholine activates specific receptor-operated channels which are less sensitive to calcium antagonists than K(+)-activated voltage-dependent channels. Moreover, acetylcholine-induced contractions in this model do not appear to be the result of calcium release from the sarcoplasmic reticulum since ryanodine failed to attenuate contractions.
Tanz
R D
RD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Nayler
W G
WG
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013552:Swine
D011942:Receptors, Adrenergic, alpha; D011189:Potassium Chloride; D001285:Atropine; D004110:Diltiazem; D011738:Pyrilamine; D009543:Nifedipine; D000109:Acetylcholine; D011224:Prazosin; D008784:Methysergide