MUSCARINIC ANTAGONISM OF THE EFFECTS OF A PHOSPHODIESTERASE INHIBITOR (METHYLISOBUTYLXANTHINE) IN EMBRYONIC CHICK VENTRICLE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (2) , 348-356
Abstract
Methylisobutylxanthine (MIX) augmented contractions and Ca++-dependent action potentials in ventricles isolated from embryonic and hatched chicks. Acetylcholine (ACh) inhibited these effects of MIX. In ventricles from chicks on the 18th incubation day, cAMP content was increased to .apprx. 150% of basal after 3 min in 3 .times. 10-4 M MIX. ACh (10-6 M) did not reduce the cAMP accumulation caused by MIX, but the increase in twitch tension was abolished. ACh 10-4 M blocked the MIX-induced increases in both twitch tension and cAMP. ACh antagonizes the effects of MIX both by blocking the action of elevated cAMP and in higher concentrations and by inhibiting the accumulation of cAMP. In homogenates of chick ventricle, ACh did not stimulate phosphodiesterase activity or block the inhibition of phosphodiesterase by MIX. Inhibition of cAMP accumulation by higher concentrations of ACh may be due to inhibition of adenylate cyclase activity. Neither 10-6 nor 10-4 M ACh reduced basal cAMP content, basal adenylate cyclase is presumably not affected by ACh. MIX may indirectly increase adenylate cyclase activity by antagonizing an inhibitory effect of endogenous adenosine. ACh may interfere with this effect of MIX, thereby facilitating the inhibition of adenylate cyclase by adenosine.