Chronic ethanol exposure inhibits ATP-stimulated but not KCl-stimulated dopamine release in PC 12 cells.

The functional significance of the ethanol-induced alterations in intracellular concentration of free calcium ([Ca++]i) was determined in PC 12 cells by measuring agonist-stimulated dopamine (DA) release after ethanol exposure. ATP and KCl produced a concentration-dependent release of DA, which was linearly related to the net increase in [Ca++]i, but different relationships were observed with ATP and KCl. Acute addition of 150 mM ethanol inhibited KCl-stimulated release of DA, but did not alter the response to ATP. In contrast, a 4-day exposure to 150 mM ethanol led to a reduction in ATP-evoked DA release without altering the response to KCl. Furthermore, a 7-day treatment with 25 mM ethanol also decreased the response to ATP. Acute and chronic ethanol exposures, however, did not alter the relationships between DA release and the increase in [Ca++]i observed with ATP and KCl. The data indicate that acute and chronic ethanol treatments have differential effects on the responses to extracellular ATP and KCl and alter DA release primarily by altering the calcium influx stimulated by agonists.