Myocardial inositoltrisphosphate is depressed by dibutyryl cAMP. An experimental study in the isolated working rat heart

Abstract

A possible interrelation between IP3 and cAMP was studied in rat myocardium through circumvention of the receptor mediated stimulatory step of adenylyl cyclase by the administration of dibutyryl cAMP (db-cAMP). Changes in IP3 and cyclic nucleotide contents were correlated to changes in contractility after 40 min of beta- and alpha-adrenergic stimulation. Rat hearts (n = 23) were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus as a working preparation. The hearts were allocated to perfusion as control (n = 6); or with phenylephrine (10(-6) mol L-1, n = 6); (-)-isoproterenol (10(-6) mol L-1, n = 6); db-cAMP (2 x 10(-4) mol L-1, n = 5). All hearts were freeze-clamped after 40 min of perfusion. Phenylephrine produced a slow increase in maxdP/dt reaching a maximal value after 10 min (P < 0.05); thereafter it decreased, reaching the control level at 30 min. Isoproterenol perfusion resulted in an early (20 s) increase in maxdP/dt (P < 0.05). Over the next 10s maxdP/dt decreased markedly reaching an inflection point at 30 s. Thereafter only a slow increase during the rest of the perfusion was seen. Dibutyryl cAMP increased maxdP/dt slowly during the whole perfusion period reaching maximum after 40 min. Cyclic-AMP was increased by 21% after 40 min of phenylephrine perfusion while the corresponding increases by isoproterenol and db-cAMP were 131 and 105%, respectively (P < 0.05). Phenylephrine increased IP3 content to the same extent as isoproterenol perfusion (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)