Effects of chronic exposure to ethanol on the prostaglandin E1 receptor-mediated response and binding in a murine neuroblastoma clone (N1E-115).

With the use of cultured murine neuroblastoma cells (clone N1E-115), the authors studied the effects of chronic ethanol on prostaglandin E, (PGE1)-mediated cyclic AMP formation, adenylate cyclase activity and [3H]PGE1 binding. Whereas acute exposure of these cells to ethanol potentiates the PGE1 response, exposure of cells, for as little as 1 day, to 100 mM ethanol resulted in a diminished responsiveness to PGE1 compared with that in acutely treated cells. This apparent tolerance was well developed by day 4, and, by day 7, treated cells had a diminished response to PGE1 when assayed in the absence of ethanol. To achieve the same level of PGE1-mediated cyclic AMP synthesis as acutely exposed cells, chronically exposed cells required higher concentrations of ethanol. With 7 to 10 days of treatment, there was a modest (10-13%) increase in basal, PGE1- and forskolin-stimulated adenylate cyclase activity in membranous preparations, a 28 to 40% increase in high-affinity [3H]PGE1 binding to membranes with no change in Kd or in the ability of 5'-guanylimidodiphosphate to reduce this binding and a 155% increase in [3H]PGE1 binding to intact cells with no change in Kd. Thus, chronic exposure of N1E-115 cells to ethanol resulted in tolerance to its effects on the PGE1 receptor system, and this tolerance was accompanied by apparently paradoxical changes in PGE1-stimulated cyclic AMP synthesis and [3H]PGE1 binding.