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.
Willuweit
B
B
Rudolf-Buchheim-Institut für Pharmakologie, Giessen, Federal Republic of Germany.
Aktories
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K
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000097:blood; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000097:blood*; D006160:Guanosine Triphosphate / Q000097:blood / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D011942:Receptors, Adrenergic, alpha; D006160:Guanosine Triphosphate; D006493:Heparin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D004837:Epinephrine