Platelet functions after intravenous administration in man of cyclic-AMP and related drugs

Platelet function has been investigated in human volunteer subjects after intravenous administration of cyclic-AMP and of its dibutyryl derivative. Activators of platelet adenyl cyclase, such as isoprenaline and glucagon, and inhibitors of phosphodiesterase, such as dipyridamole and aminophylline, have been similarly investigated relating any effect on platelet function to the variation of the levels of cyclic-AMP in platelet-rich plasma (PRP). Dibutyryl cyclic-AMP and, to a lesser extent, cyclic-AMP infusions were followed by a consistent inhibition of platelet aggregation induced by ADP, collagen, and adrenaline. Platelet retention to glass beads and the release of platelet factor 4 were also decreased; the standardized bleeding time, platelet count, and the availability of platelet factor 3 were not modified. Isoprenaline inhibited platelet aggregation, and the effect was correlated in time and magnitude with a slight increase of cyclic-AMP in PRP. Glucagon, aminophylline and dipyridamole had no effect on platelet count aggregation and cyclic-AMP. However, dipyridamole was inhibitory when given in combination with dibutyryl cyclic-AMP in doses which are ineffective when used separately. Our results suggest an in vivo relationship between inhibition of platelet aggregation and the increase of cyclic-AMP in PRP.