Effects of adenosine 3′:5′-monophosphate and platelet aggregation on thromboxane biosynthesis in human platelets

Abstract

The prostaglandin (PC) endoperoxides, PGGs and PGHz [l], and thromboxane (TX)A, [2] cause rapid aggregation and induce the release reaction in human platelets. Aggregating agents, such as collagen and thrombin, stimulate release of arachidonic acid from platelet phospholipids. This leads to synthesis of endoperoxides, thromboxanes, prostaglandins and hydroxy acids [3-51. Elevation of adenosine 3’: 5’-monophosphate (cyclic AMP) levels in platelets prevents aggregation [6-8] and the simultaneous production of TXBz [9-121. Two mechanisms for the inhibition of thromboxane formation have been proposed: (1) Inhibition of prostaglandin endoperoxide synthase (EC 1.14.99.1) [9]; (2) Inhibition of arachidonic acid release from platelet phospholipids [lo121. In the latter reports no inhibition of prostaglandin endoperoxide synthase was observed [lo-121. We have therefore reinvestigated the effects of cyclic AMP on arachidonic acid release and on the conversion of arachidonic acid to TXBs. The results suggest that elevation of cyclic AMP levels inhibits both of these reactions in platelets and that the inhibitory effect of cyclic AMP on TXBz formation from arachidonic acid is not direct but secondary to inhibition of platelet aggregation.