REGULATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS ON HUMAN NEUROBLASTOMA-CELLS DURING DIFFERENTIATION

Neuronal nicotinic acetylcholine receptors are expressed on a variety of cells in the nervous system where they play key roles in synaptic t ransmission and information transfer. Little is known, however, about the molecular mechanisms that control their expression, distribution, and function during nervous system development. We have investigated t he control of expression during differentiation of one class of acetyl choline receptors that bind a-bungarotoxin of human neuroblastoma cell s. We report that induction of differentiation of SH-SY5Y, SK-n-SH or IMR-32 cells by the phorbol ester 12-O-tetradecanoyl phorbol 13-myrist ate (10 nM, TPA) or by retinoic acid resulted in as much as a 70% decl ine in alpha-bungarotoxin receptors on the cells. The response to the phorbol ester was blocked by the protein kinase C inhibitors staurospo rine and bisindolylmaleimide. The decrease in receptors induced by 10 mu M retinoic acid was not affected by either agent. However, response s to lower (10 nM) concentrations of retinoic acid were blocked by sta urosporine but not bisindolyl-maleimide, suggesting a dual mechanism o f action for retinoic acid in regulating acetylcholine receptors. It a ppears that acetylcholine receptors on neuroblastoma cells are regulat ed during differentiation by both protein kinase C-dependent and -inde pendent mechanisms.