Effects of acetaldehyde condensation products on human platelet aggregation.
Condensation products (CP) of the ethanol metabolite, acetaldehyde, and endogenous amines, such as dopamine and serotonin, have been proposed to be effectors of some symptoms of chronic ethanol use. Since hemostatic defects are known to occur in chronic ethanol use, the effects of CP on in vitro human platelet aggregation responses induced by several agents were determined. Both isoquinoline and beta carboline type CP significantly inhibited aggregation responses induced by epinephrine, with the concentrations to produce 50% inhibition ranging from 8-347 uM. The beta-carbolines significantly inhibited ADP-induced aggregation and also inhibited aggregation induced by collagen or arachidonic acid, but at high concentrations. Effects on epinephrine aggregation and ADP aggregation were reversible. Potential mechanisms of the inhibitory effects were briefly examined. Concomitant use of the phosphodiesterase inhibitor theophylline potentiated the effect of some but not other CP, possibly indicating an involvement of cyclic AMP. Concomitant use of the non-specific beta-adrenergic inhibitor propranolol had no effect on CP inhibition, indicating that CP probably do not stimulate platelet adenylyl cyclase-coupled beta 2-adrenoceptors. Thus, general inhibition by CP of platelet responses in the circulation is unlikely, except, possibly, for epinephrine-induced aggregation, because of the high concentrations of CP required. However, local regulation of platelet responses by release of stored CP during aggregation is possible since CP are stored in platelet dense granules.
D000079:Acetaldehyde / Q000378:metabolism / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000437:Alcoholism / Q000097:blood* / Q000378:metabolism; D002243:Carbolines / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D002243:Carbolines; D007546:Isoquinolines; D000431:Ethanol; D000244:Adenosine Diphosphate; D011433:Propranolol; D013806:Theophylline; D000079:Acetaldehyde; D004837:Epinephrine