EFFECT OF CYCLIC 3',5'-GUANOSINE MONOPHOSPHATE ON HUMAN PLATELET-FUNCTION

Abstract

The relation of cyclic[c]GMP to platelet function was studied by investigating the influence of this compound and its N2,O2''-dibutyryl derivative (DBcGMP) on platelet aggregation and the release reaction. Both cGMP and dibutyryl cGMP enhanced to an equal extent platelet aggregation induced by epinephrine or by chick skin collagen .alpha.1 chain. The platelet release reaction, as measured by the release of [14C]-labeled 5-hydroxytryptamine (serotonin) was also enhanced by the cyclic nucleotides. Both compounds were also able to partially overcome the inhibitory effect of N6,O2''-dibutyryl AMP (DBcAMP), prostaglandin E1 and theophylline. The effect of DBcGMP did not result from contamination with 5''-GMP. Butyric acid and 5''-GMP, either alone or in combination, had no detectable effect on platelet function. The in vitro effect of DBcGMP and cGMP was not dependent on preincubation of platelets with the compounds. Their effect was apparently mediated by direct action on the platelet membranes. These data were consistent with previous observations that the platelet aggregating agents (epinephrine, ADP, collagen and chick collagen .alpha.1 chains) caused an increase in the content of GMP and supported the hypothesis that platelet aggregation was favored by an increase in cGMP.