Intracellular actions of 5‐hydroxytryptamine on the bivalve myocardium. II. Cyclic nucleotide‐dependent protein kinases and microsomal calcium uptake

The effects of cyclic AMP, cyclic AMP‐induced phosphorylation, and 5‐hydroxytryptamine (5HT) on calcium uptake by bivalve heart microsomes were investigated. Cyclic AMP‐dependent and cyclic GMP‐dependent protein kinases were purified from Macrocallista nimbosa ventricles. The cyclic AMP‐dependent preparation readily phosphorylates myocardial cell proteins in both the soluble and microsomal fractions. The cyclic AMP‐mediated phosphorylation of microsomal protein augments microsomal calcium uptake; but 5HT and cyclic AMP also induce a similar increase directly. The protein kinase activity indigenous to the microsomal preparation was not increased by cyclic AMP. In many molluscan ventricles, 5HT increases intracellular cyclic AMP and simultaneously enhances muscle contractility by altering the amount of intracellular calcium available for contraction. Therefore, if cyclic AMP acts as a second messenger and mediates the effects of 5HT, the nucleotide should augment, directly or indirectly, the amount of membrane associated calcium. This study suggests that cyclic AMP can mediate 5HT action either by the activation of a cyclic AMP‐dependent protein kinase, or by a direct modification of the amount of membrane associated calcium.