Sensitivity of Ca-dependent slow action potentials to methacholine is induced by phosphodiesterase inhibitors in embryonic chick ventricles.
Choline esters fail to depress developed tension or the maximum upstroke velocity (Vmax) of slow action potentials in embryonic chick ventricles, but they inhibit the stimulatory effect of the phosphodiesterase inhibitor methylisobutylxanthine (MIX). The mechanism by which the choline ester methacholine (MCh) counteracts the effects of MIX was examined in ventricular myocardium obtained from 7-day-old embryonic chicks. Four possible hypotheses were 1) that the physiological response to MCh is mediated by cyclic GMP, the production of which is potentiated by MIX; 2) that MCh acts by a mechanism independent of cyclic nucleotides; 3) that the binding of MIX to adenosine receptors induces sensitivity to MCh; or 4) that MCh acts by depressing basal cyclic AMP levels. Interactions between MCh, Angiotensin II and a nonmethylxanthine phosphodiesterase inhibitor (Ro 7-2956) were assessed by measuring tissue levels of cyclic nucleotides and the Vmax of slow action potentials. MCh significantly reduced the basal cyclic AMP level of embryonic chick ventricles, despite having no physiological effect. The results favor the final hypothesis and imply that MCh effects are mediated by inhibition of adenylate cyclase activity. The physiological response of the myocardium to a reduction in basal adenylate cyclase activity appears to be dependent on the initial tissue level of cyclic AMP.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology*
D007093:Imidazoles; D008688:Methacholine Compounds; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; D016210:Methacholine Chloride; D000804:Angiotensin II; C100165:4-((3,4-dimethoxyphenyl)methyl)-2-imidazolidinone; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine