Thrombin-induced platelet prostaglandin and cyclic AMP production and a possible intrinsic modulation of platelet function.
In previous studies, we observed an increase in intracellular cyclic AMP in platelets during thrombin-induced nucleotide and calcium release. Our present work suggests that platelet prostaglandins are directly involved in this phenomenon. Washed human platelets were incubated at 37 degrees C with human thrombin for times ranging between 5 s and 5 min. The release of nucleotides and calcium in response to thrombin, determined spectrophotometrically, reached 40-60% of maximal plateau levels by 5 s, 70-80% by 10 s, and 90-100% by 15 s. The production and secretion of prostaglandin E (PGE), measured by radioimmunoassay, parelleled this rapid time course. After 10 s, however, the amount of extracellular PGE began to decrease, continuing to do so through 5 min of incubation. Intracellular cyclic AMP accumulation, determined by radioimmunoassay, lagged behind the time course of nucleotide and calcium release, and that of PGE secretion, by several seconds. This lag in cyclic AMP accumulation appeared to correlate closely with the disappearance of PGE from the supernate in the same platelet samples. In view of the inhibitory effects of cyclic AMP and PGE on platelet release and aggregation, these interrelated time course curves suggest the existence within platelets of a mechanism for the modulation of platelet activity.
D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009711:Nucleotides / Q000097:blood / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D011458:Prostaglandins E / Q000097:blood / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D013917:Thrombin / Q000008:administration & dosage / Q000494:pharmacology*
D009711:Nucleotides; D011453:Prostaglandins; D011458:Prostaglandins E; D000242:Cyclic AMP; D013917:Thrombin; D002118:Calcium