Diverse effects of ethanol on Ca2+ entry and subsequent aggregation of platelets.
Although alcohol is known to inhibit platelet aggregation, and transplasmalemmal Ca(2+) entry is profoundly involved in platelet aggregation, there has been limited knowledge about the relationship between alcohol and Ca(2+) entry. The purpose of this study was to determine whether and how ethanol in vitro affects Ca(2+) entry through different pathways and the subsequent aggregation of platelets. Thapsigargin, 1-oleoyl-2-acetyl-sn-glycerol (OAG), and thrombin were used to stimulate human platelets. Ca(2)(+) entry and the subsequent aggregatory responses of platelets were measured by spectrofluorometry using fura-2/AM as an indicator and the light transmission method, respectively. Thapsigargin-induced Ca(2+) entry and the following platelet aggregation were significantly inhibited by ethanol at concentrations of 0.5% or more. OAG-induced Ca(2+) entry was significantly augmented by ethanol at concentrations of 0.5% or more, whereas platelet aggregation by OAG was significantly inhibited by ethanol at concentrations of 0.5 % or more. Thrombin-induced Ca(2+) entry was not significantly affected by ethanol up to 2%, whereas platelet aggregation by thrombin was markedly inhibited by ethanol at concentrations of 0.5% or more. Thrombin-induced Ca(2+) entry in the presence of SKF-96365 was augmented by pretreatment with ethanol. Ethanol in vitro showed diverse effects on the different Ca(2+) entry pathways of platelets, whereas aggregatory responses induced by activation of the different Ca(2+) entry pathways of platelets were all inhibited by ethanol. These results suggest that ethanol inhibits platelet aggregation mainly via a mechanism(s) other than transplasmalemmal Ca(2+) entry.
Marumo
Mikio
M
Department of Environmental and Preventive Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Wakabayashi
Ichiro
I
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology
D000431:Ethanol; D002118:Calcium