Concentration-dependent desensitization of isolated porcine coronary arterial segments to acetylcholine

Arch Int Pharmacodyn Ther. 1991 Jul-Aug;312:110-25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Atropine / pharmacology
  • Coronary Vessels / drug effects*
  • Diltiazem / pharmacology
  • Dose-Response Relationship, Drug
  • Methysergide / pharmacology
  • Muscle Contraction / drug effects*
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Nifedipine / pharmacology
  • Potassium Chloride / pharmacology
  • Prazosin / pharmacology
  • Pyrilamine / pharmacology
  • Receptors, Adrenergic, alpha / drug effects
  • Swine


  • Receptors, Adrenergic, alpha
  • Potassium Chloride
  • Atropine
  • Diltiazem
  • Pyrilamine
  • Nifedipine
  • Acetylcholine
  • Prazosin
  • Methysergide