Pyrrolidine dithiocarbamate prevents ethanol-induced elevation of [Ca2+]i in cultured canine cerebral vascular smooth muscle cells.

Pyrrolidine dithiocarbamate (PDTC) has been shown to block nuclear transcription factor (NF-kappaB) activation induced by a wide range of stimuli in different cell lines. NF-kappaB is a common element of the promoter region of inflammatory cytokines which can be stimulated by ethanol. Recently, we have shown that PDTC can ameliorate cerebrovascular damage, brain cortical damage, leukocyte adhesion and rolling, and stroke induced by ethanol. We, therefore, tested the effects of preincubation with PDTC on alcohol-induced changes in intracellular free calcium ions ([Ca2+]i) in cultured canine cerebral smooth muscle cells. These vascular cells, chronically treated with ethanol (10-100 mM) for 24 and 72 h, exhibited concentration-dependent rises in [Ca2+]i. PDTC (0.1 microM) itself failed to influence resting levels of [Ca2+]i in these vascular muscle cells. PDTC (0.1 microM) pretreatment, however, inhibited completely the elevations in [Ca2+]i induced by chronic ethanol (10-100 mM). The present results suggest that ethanol-induced production of reactive oxygen species and elevation of [Ca2+]i in cultured canine cerebral vascular smooth muscle cells triggers induction of transcription factor NF-kappaB, which could play an important role in alcohol-induced brain damage and stroke.