Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated?
Parathyroid hormone (PTH) is a polypeptide which in different in vitro systems raises intracellular cyclic AMP (cAMP) levels via adenyl cyclase activation and stimulates Ca2+ transport across cell membranes. We tested whether, on the basis of this mechanism, PTH would inhibit human platelet aggregation. The latter was tested in vitro by a photometric technique. Platelet aggregation induced by the calcium ionophore A 23187 was inhibited by PTH at concentrations (0.5-3 USP U/ml) similar to those effective in other in vitro systems. Higher concentrations of PTH were required to prevent aggregation initiated by adenosine-5'-diphosphate, arachidonic acid, or platelet-aggregating factor. The terminal synthetic fragment 1-34 b PTH was ineffective against all aggregation stimuli. The antiaggregating effect of PTH was potentiated by verapamil and theophylline and was additive to that of PGI2. However, PTH did not appear to increase platelet cAMP levels and was not counteracted by an inhibitor of platelet adenyl cyclase. It is therefore unlikely that PTH inhibits platelet aggregation through an adenyl cyclase stimulated increase of cAMP. Since PTH levels are markedly increased in uremic plasma, it might contribute to the defective platelet function and the bleeding tendency frequently occurring in uremic patients.
D000262:Adenylyl Cyclases / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D014511:Uremia / Q000097:blood; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D000001:Calcimycin; D013929:Thromboxane B2; D013806:Theophylline; D014700:Verapamil; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium