Islet-activating protein impairs alpha 2-adrenoceptor-mediated inhibitory regulation of human platelet adenylate cyclase.
Human platelet adenylate cyclase is stimulated by prostaglandin E1 (PGE1) and inhibited by adrenaline acting via alpha 2-adrenoceptors. Both hormonal factors increase GTP hydrolysis in platelet membranes by stimulation of a high affinity GTPase. The influence of the Bordetella pertussis toxin, islet-activating protein (IAP), was studied on adrenaline and PGE1-induced GTPase stimulation and on adrenaline-induced adenylate cyclase inhibition. Pretreatment of platelet membranes with IAP greatly reduced the adrenaline-induced inhibition of the platelet adenylate cyclase. At similar concentrations of the toxin, stimulation of GTP hydrolysis caused by adrenaline was impaired. In contrast, pretreatment of platelet membranes with IAP had no effect on stimulation of GTP hydrolysis by the adenylate cyclase-stimulating agent, PGE1, both when studied alone or in combination with adrenaline. On the other hand, cholera toxin reduced the PGE1-induced GTPase stimulation but did not affect the adrenaline-stimulated GTP hydrolysis. The data indicate that there are two separate GTP-hydrolyzing systems in human platelet membranes and that cholera toxin and pertussis toxin selectively affect stimulation of GTP hydrolysis by hormones that stimulate and inhibit adenylate cyclase, respectively.
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil; D001426:Bacterial Proteins / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology*; D004837:Epinephrine / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000097:blood; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D037342:Pertussis Toxin; D011458:Prostaglandins E / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001426:Bacterial Proteins; D011458:Prostaglandins E; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D000527:Alprostadil; D004837:Epinephrine