Heparin and heparinoids impair adrenaline and platelet-activating factor but not thrombin-induced inhibition of adenylate cyclase and stimulation of GTP hydrolysis in human platelet membranes.

Abstract

The effects of heparins and heparinoids were studied on adenylate cyclase and GTPase activities in human platelet membranes. Inhibition of adenylate cyclase by adrenaline and platelet activating factor was completely abolished by heparin at 1 microgram/ml. At similar concentration heparin blocked the stimulation of high affinity GTPase(s) by these hormonal factors. In contrast, heparin (up to 30 micrograms/ml) did not abolish adenylate cyclase inhibition and stimulation of GTP hydrolysis by thrombin in the absence of antithrombin III. In the presence of antithrombin III, thrombin action on adenylate cyclase was blocked by unfractionated and high molecular weight heparin at 0.1 microgram/ml. Low molecular weight heparins and pentosanpolysulfate were less or not effective. In contrast, all high and low molecular weight heparins tested were almost equally potent in inhibiting adrenaline-induced inhibition of adenylate cyclase in the absence of antithrombin III. The data indicate that heparins discriminate platelet activating factor and adrenaline-induced inhibition of adenylate cyclase from the inhibitory action of thrombin and delineate different structural requirements for the interaction of heparins with the adenylate cyclase system and antithrombin III.