Stimulation of prostaglandin E1 binding to human blood platelet membrane by insulin and the activation of adenylate cyclase.
Incubation of human platelet-rich plasma with physiological amounts of insulin resulted in the increase of the binding of prostaglandin E1 by more than 2-fold when compared to the control platelets. Scatchard analysis of the binding of the prostaglandin to the hormone-treated platelets showed that the increased binding was due to the increase of receptor numbers rather than the increase of affinity of the binding sites. The membranes prepared from the insulin-treated platelets also showed similar enhanced binding of the prostaglandin. However, addition of insulin directly to the membranes isolated from the platelets which had not been previously incubated with the hormone failed to show any effect. This increased binding of the prostanoid to the membranes prepared from the insulin-treated platelets resulted in the stimulation of adenylate cyclase by more than 2-fold when compared with the control of membrane preparation by the prostaglandin alone. In contrast, treatment of platelets with the hormone which increased the prostanoid binding to these cells did not influence the cyclic AMP phosphodiesterase activity of either the membrane or cytosolic fraction. The increase in the cellular level of cyclic AMP by prostaglandin E1 was 2-fold greater in the hormone-treated cells than in the case of untreated platelets stimulated by the agonist alone. The incubation of platelet-rich plasma with insulin, as expected, decreased the amount of prostaglandin E1 needed to inhibit platelet aggregation by more than 50% when compared to the control platelets.
Kahn
N N
NN
Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York 10467.
Sinha
A K
AK
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood; D000262:Adenylyl Cyclases / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000527:Alprostadil / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D010974:Platelet Aggregation; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology
D007328:Insulin; D011982:Receptors, Prostaglandin; D013004:Somatostatin; D004815:Epidermal Growth Factor; D000324:Adrenocorticotropic Hormone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D000527:Alprostadil