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 intr acellular 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 relea se of DA, which was linearly related to the net increase in [Ca++]i, b ut different relationships were observed with ATP and KCl. Acute addit ion 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 exposur es, however, did not alter the relationships between DA release and th e increase in [Ca++]i observed with ATP and KCl. The data indicate tha t acute and chronic ethanol treatments have differential effects on th e responses to extracellular ATP and KCl and alter DA release primaril y by altering the calcium influx stimulated by agonists.