CILIARY NEUROTROPHIC FACTOR REGULATES NICOTINIC ACETYLCHOLINE-RECEPTORS ON HUMAN NEUROBLASTOMA-CELLS

We have investigated the effects of several neurokine/cytokine family members on the level of alpha-bungarotoxin-binding to neuronal nicotin ic acetylcholine receptors. Exposure of human neuroblastoma cells (SH- SY5Y and IMR-32) to ciliary neurotrophic factor (CNTF), leukemia inhib itory factor or oncostatin-M resulted in a 30-40% decline in alpha-bun garotoxin receptors on the cells with no decrease seen in either musca rinic acetylcholine receptors or in L-type Ca2+ channels. The level of nicotinic receptor was not affected by the related cytokine, interleu kin-6. Treatment of IMR-32 cells with 40 pM CNTF produced a half-maxim al decrease of alpha-bungarotoxin binding which compared well with the affinity estimated from binding of I-125- CNTF (K-i approximate to 40 pM) and the concentration causing c-fos activation in SH-SY5Y cells, as detected by nuclear run-on assays (60-120 pM). Previous results hav e indicated that the differentiating agents, phorbol esters and retino ic acid, also decrease nicotinic receptor numbers. Here the effects of CNTF, which did not induce neural differentiation, were enhanced by d ifferentiation with 12-O-tetradecanoylphorbol 13-acetate (10 nM) and p revented by retinoic acid (10 mu M). Therefore, the response of neurob lastoma cells to cytokines may be under developmental control. These c ells offer a system to examine cytokine responses and signal transduct ion mechanisms during neural development. Copyright (C) 1996 Elsevier Science Ltd.