Dissociation of 5-hydroxytryptamine effects on myocardial contractility and cyclic AMP accumulation.

1 5-Hydroxytryptamine increased the contractility of the isolated rat atrium and produced a small rise in cyclic 3',5'-adenosine monophosphate (cyclic AMP) accumulation in rat heart slices. These effects were similar to those of tyramine.2 Incubation with phenoxybenzamine prevented the inotropic effect of 5-hydroxytryptamine but did not inhibit the rise in cyclic AMP accumulation.3 A single injection of reserpine 24 h before the experiment did not inhibit the inotropic effect of 5-hydroxytryptamine but prevented the rise in cyclic AMP accumulation.4 It is concluded that in the rat 5-hydroxytryptamine increases cardiac contractility chiefly by a direct effect which is blocked by phenoxybenzamine, whereas it increases myocardial cyclic AMP accumulation indirectly by releasing endogenous catecholamines. Cardiac contractility may thus be increased without a rise in cyclic AMP accumulation, and cyclic AMP accumulation may be increased without a rise in contractility.