Effects of ethanol exposure on neuropeptide-stimulated calcium mobilization in N1E-115 neuroblastoma.

The effects of acute and chronic (100 mM for 7 days) ethanol exposures on resting intracellular free calcium, [Ca2+]i as well as bradykinin and neurotensin mediated [Ca2+]i mobilization were determined in intact N1E-115 neuroblastoma. [Ca2+]i was monitored fluorometrically with the calcium indicator, fluo-3/AM. Acute exposure to ethanol resulted in an inhibition of bradykinin mediated [Ca2+]i mobilization with significant effects observed only at 400 mM ethanol. Neurotensin mediated [Ca2+]i mobilization was not significantly affected by any of the ethanol concentrations tested. Similarly, resting [Ca2+]i (64 +/- 2 nM) was unaffected by either chronic or acute ethanol as high as 400 mM. However, chronic exposure to ethanol significantly reduced the magnitude of bradykinin mediated [Ca2+]i mobilization both in the absence and presence of extracellular [Ca2+]. In contrast, [Ca2+]i mobilization in the presence of various concentrations of neurotensin was not significantly affected by chronic ethanol exposure. The results suggest that neuropeptide mediated [Ca2+]i mobilization is relatively insensitive to the acute presence of ethanol. In addition, chronic ethanol exposure appears to have selective effects on receptor mediated [Ca2+]i mobilization because this response to bradykinin, but not neurotensin, was significantly reduced in cells exposed to ethanol. The results also suggest that the reduction in bradykinin stimulated [Ca2+]i mobilization in chronically exposed cells is due in part to an inhibition of the release of intracellularly bound [Ca2+].