Alterations in intracellular calcium homeostasis and platelet aggregation induced by ethanol.
The in vitro effects of ethanol on intracellular Ca(2+) homeostasis and tyrosine phosphorylation have been investigated in human platelets in order to clarify the cellular mechanisms underlying its described anti-aggregant effects. Ethanol (1-50 mM) reduced, in a dose-dependent manner, the rate and amplitude of aggregation and attenuated the phosphotyrosine content both induced by 0.1U/ml of the physiological ligand, thrombin. Thrombin-induced Ca(2+) entry to the cytosol was significantly reduced, and capacitative Ca(2+) entry (CCE) significantly altered, by 50 mM ethanol, so that ethanol reduces CCE mediated by depletion of the 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ)-sensitive store but enhances CCE induced by the TBHQ-insensitive pool. In conclusion, we provide considerable evidence that ethanol reduces thrombin-induced aggregation, which is likely a result of a significant inhibition of Ca(2+) entry, as well as a reduction in the activity of protein tyrosine kinases.
Rosado
Juan A
JA
Department of Physiology, University of Extremadura, 10071 Cáceres, Spain. jarosado@unex.es
Núñez
Ana M
AM
Pariente
José A
JA
Salido
Ginés M
GM
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood*; D000431:Ethanol / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D019000:Phosphotyrosine / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D019000:Phosphotyrosine; D000431:Ethanol; D013917:Thrombin; D002118:Calcium