Effects of acetaldehyde condensation products on human platelet aggregation.

Alcohol and drug research Pub Date : 1987-01-01
M B Given, G L Longenecker
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Abstract

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.

乙醛缩合产物对人血小板聚集的影响。
乙醇代谢物乙醛和内源性胺(如多巴胺和血清素)的缩合产物(CP)被认为是慢性乙醇使用的一些症状的影响因素。由于已知长期使用乙醇会出现止血缺陷,因此我们确定了CP对几种药物诱导的体外人血小板聚集反应的影响。异喹啉和β -卡波林型CP均能显著抑制肾上腺素诱导的聚集反应,抑制浓度在8 ~ 347 μ m之间,达到50%。β -碳水化合物显著抑制adp诱导的聚集,也抑制胶原或花生四烯酸诱导的聚集,但浓度较高。对肾上腺素聚集和ADP聚集的影响是可逆的。简要探讨了其抑制作用的潜在机制。同时使用磷酸二酯酶抑制剂茶碱增强了某些CP的作用,但没有增强其他CP的作用,可能表明与环AMP有关。同时使用非特异性β -肾上腺素能抑制剂心得安对CP抑制没有影响,表明CP可能不会刺激血小板腺苷酸环化酶偶联β 2-肾上腺素受体。因此,除了肾上腺素诱导的聚集外,由于需要高浓度的CP, CP对循环中血小板反应的一般抑制是不可能的。然而,由于CP储存在血小板致密颗粒中,因此在聚集过程中通过释放储存的CP来局部调节血小板反应是可能的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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