Heparin uncouples alpha 2-adrenoceptors from the Gi-protein in membranes of human platelets.

The influence of heparin was studied on the inhibitory regulation of adenylate cyclase in human platelet membranes. Heparin blocked the adrenaline-induced inhibition of adenylate cyclase and the stimulation of GTP hydrolysis with half-maximal and maximal efficiency at 0.3 and 1-3 micrograms/ml, respectively. The effect of heparin was reversed by washing the membranes. Heparin did not change the number of alpha-adrenoceptors. In contrast, the affinity of the alpha-adrenoceptor for adrenaline was decreased in the presence of heparin. The pertussis toxin-catalysed ADP-ribosylation of the inhibitory guanine nucleotide-binding Gi-protein was not altered by heparin. Heparin also abolished the inhibition of adenylate cyclase caused by GTP itself. The data indicate that heparin can impair the hormone-induced inhibition of adenylate cyclase and the stimulation of GTP hydrolysis and suggest that the effects of heparin are caused by an action at the Gi-protein of the adenylate cyclase system.