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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. |
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