Previous studies have shown that ethanol can alter neurotransmitter release and neurosecretion; however, the mechanisms involved in these effects have not been determined. We have studied neurosecretory mechanisms and the actions of ethanol on those mechanisms in several secretory cell types. In the ACTH secreting mouse pituitary cell line, AtT-20, we have studied both calcium current and calcium-activated chloride current. Calcium current in these cells is inhibited by somatostatin and analysis of the mechanism indicates that the inhibition involves a GTP-binding protein. Calcium current in these cells is also inhibited by protein kinase C activators. Analysis of the calcium-activated chloride current in AtT-20 cells reveals that the decay kinetics are largely due to mechanisms that regulate intracellular calcium. The relationship between intracellular calcium and neurosecretion was studied in the catecholamine secreting rat chromaffin cell line, PC12. In these cells, muscarine-stimulated release of catecholamine is associated with an inositol triphosphate-induced mobilization of intracellular calcium. Ethanol inhibits both the release of neurotransmitter and the increase of intracellular calcium. The membrane mechanisms associated with secretion are also being investigated in cells from the pineal gland of the adult rat. The significance of the project derives from the fact that characterization of neurosecretory mechanisms and the actions of ethanol on those mechanisms should increase our understanding of the cellular basis of ethanol's actions in the nervous and endocrine systems.
