LONG-TERM EXPOSURE TO ETHANOL INCREASES THE NUMBER AND FUNCTION OF MUSCARINIC M1 RECEPTORS IN HUMAN NEUROBLASTOMA-CELLS

The effect of long-term ethanol exposure on muscarinic receptors was i nvestigated in human neuroblastoma SH-SY5Y cells. Exposure to 100 mM e thanol for 4 days enhanced both peak and steady-state levels of carbac hol-stimulated inositol 1,4,5-trisphosphate increase, An ethanol conce ntration of 50 mM was sufficient for an enhancement of this event. The carbachol-stimulated decrease in [H-3]inositol-labeled [H-3]phosphati dylinositol 4,5-bisphosphate and increase in [H-3]inositol trisphospha te and [H-3]inositol bisphosphate were also potentiated in ethanol-tre ated cells, which demonstrated that the receptor-stimulated activation of phospholipase C is augmented. Experiments with pirenzepine showed that carbachol-stimulated inositol 1,4,5-trisphosphate increase is med iated via M1 receptors both in ethanol-treated and control cells. Etha nol exposure for 2 or 4 days also caused an increase in [H-3]N-methyls copolamine and [H-3]quinuclidinyl benzilate binding sites and elevatio n of [H-3]pirenzepine binding, which indicated that the number of musc arinic M1 receptors is increased in ethanol-treated SH-SY5Y cells. The se results demonstrate that long-term exposure to ethanol potentiates muscarinic M1 receptor-stimulated activation of phospholipase C in SH- SY5Y cells, This is likely to be explained by an increased number of m uscarinic M1 receptors.