Inhibitory action of cyclic GMP on secretion, polyphosphoinositide hydrolysis and calcium mobilization in thrombin-stimulated human platelets.
The effect of cyclic GMP (cGMP) on human platelet activation was investigated, using its metabolically stable analogue, 8-bromo cGMP (8-bcGMP). Thrombin-induced serotonin secretion was inhibited by pretreatment with 8bcGMP in a dose-dependent manner. Production of inositol trisphosphate (IP3), a Ca2+ releaser was inhibited by 8bcGMP pretreatment of platelets. Preincubation of platelets with 8bcGMP was without effect on the basal level of cytosolic free Ca2+, measured by fluorescent indicator quin2, but suppressed its thrombin-induced enhancement independently of extracellular Ca2+. These results indicate that cGMP may be implicated in phospholipase C activation and Ca2+ mobilization (both influx through the plasma membrane and efflux from internal stores) in thrombin-activated human platelets.
D000634:Aminoquinolines; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D006152:Cyclic GMP / Q000494:pharmacology*; D003864:Depression, Chemical; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000097:blood*; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
D000634:Aminoquinolines; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D012701:Serotonin; D003994:Bucladesine; C035738:Quin2-acetoxymethyl ester; D013917:Thrombin; D006152:Cyclic GMP; D002118:Calcium