Inhibition by ADP of prostaglandin induced accumulation of cyclic AMP in intact human platelets.
The influence of extracellular ADP on cyclic AMP accumulation within intact human platelets was studied. ADP inhibited the increase in cyclic AMP which occurs when platelets are exposed to prostaglandin E1 or I2. The degree of inhibition varied in the range 70-95% , and was half maximal at ADP concentrations of between 0.3 and 2 microM. Other naturally occurring diphosphates, i.e. GDP, IDP and UDP, were at least 100 fold less effective than ADP, and UDP at 1mM partially reversed the effect of ADP. The effect by ADP was completely reversed by ATP, but only attenuated to a minor degree of 10 mM EDTA. Increasing concentrations of ADP caused a progressive degree of inhibition of cyclic AMP accumulation, and the kinetics of this inhibition were compatible with a simple saturable process with no cooperativity. ADP added 10 seconds after prostaglandin E1 blocked cyclic AMP accumulation within 1-2 seconds, and addition of ATP after ADP and prostaglandin I2 relieved the inhibition due to ADP within 2-3 seconds. The action of ADP was blocked by sulphydryl reagents including N-substituted maleimides, cytochalasin A, NBD chloride and p-mercuribenzene sulphonate. The data were considered to be consistent with mediation of the ADP effect through a sulphydryl-bearing specific extracellular receptor coupled to the adenylate cyclase.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood*; D003572:Cytochalasins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D010663:Phenylmercury Compounds / Q000494:pharmacology; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E / Q000037:antagonists & inhibitors*
D003572:Cytochalasins; D008301:Maleimides; D010663:Phenylmercury Compounds; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; C031218:cytochalasin A; C031219:4-mercuribenzene sulfonate; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D000242:Cyclic AMP