Inhibition of ethanol-induced platelet activation by agents that elevate cAMP.
Ethanol activates phosphoinositide-specific phospholipase C in human platelets resulting in the mobilization of intracellular calcium and shape change (Arch. Biochem. Biophys. 260, 480-492, 1988). Preincubation of platelets with agents that increase levels of cAMP (i.e., forskolin, prostacyclin) inhibited these responses to ethanol in a concentration- and time-dependent manner. The inhibitory effect was potentiated by the phosphodiesterase inhibitor, isomethybutylxanthine. When added after ethanol, these agents also reversed platelet shape change and lowered cytosolic free calcium to basal levels. The results demonstrate a direct inhibitory effect of cAMP on the ethanol-induced activation of phospholipase C.
Rubin
R
R
Department of Pathology and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Hoek
J B
JB
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000097:blood; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood*; D011464:Epoprostenol / Q000494:pharmacology*; D000431:Ethanol / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors
D010975:Platelet Aggregation Inhibitors; D005576:Colforsin; D000431:Ethanol; D011464:Epoprostenol; D000242:Cyclic AMP; D002118:Calcium