EFFECTS OF ETHANOL ON BASAL AND PROSTAGLANDIN E1-INDUCED INCREASES INBETA-ENDORPHIN, RELEASE AND INTRACELLULAR CAMP LEVELS IN HYPOTHALAMICCELLS

Our recent studies determining the effect of cAMP-elevating agents for skolin and dibutyryl cAMP on ethanol-induced immunoreactive beta-endor phin (IR-beta-EP) release from hypothalamic cells in primary cultures suggested the possibility that both stimulatory and adaptive secretory responses of beta-EP neurons after ethanol exposure may involve the c AMP system. To determine further the role of cAMP, the effects of pros taglandin E1 (PGE1) on basal and ethanol-regulated IR-beta-EP secretio n and cAMP productions were determined in primary cultures of hypothal amic cells. The results presented in this study show that a 50 mM dose of ethanol, which is within the EC50 dose of ethanol required to elev ate IR-beta-EP release from hypothalamic cells, increased cellular lev els of cAMP and elevated IR-beta-EP release simultaneously from the cu ltured neurons for a period of 6 hr. The cAMP and IR-beta-EP secretory responses developed desensitization to ethanol challenge after 24 hr of constant ethanol incubation. The cAMP-elevating agent PGE1 increase d the cellular content of cAMP and IR-beta-EP release in a dose-depend ent manner. The EC50 dose of PGE1 for elevation of IR-beta-EP and cAMP was similar to 0.5 mu M. As with ethanol, chronic treatment with PGE1 desensitized the cAMP and IR-beta-EP responses of hypothalamic neuron s to PGE1. Acute exposure to ethanol increased the PGE1-stimulated lev els of cAMP and IR-beta-EP, whereas chronic exposure to ethanol result ed in diminished cAMP responses to PGE1. These data provide evidence t hat the cAMP system may be involve in controlling hypothalamic beta-EP secretion, as well in regulating the stimulatory and adaptive respons es of beta-EP neurons to ethanol.