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 nicotinic acetylcholine receptors. Exposure of human neuroblastoma cells (SH-SY5Y and IMR-32) to ciliary neurotrophic factor (CNTF), leukemia inhibitory factor or oncostatin-M resulted in a 30-40% decline in alpha-bungarotoxin receptors on the cells with no decrease seen in either muscarinic acetylcholine receptors or in L-type Ca2+ channels. The level of nicotinic receptor was not affected by the related cytokine, interleukin-6. Treatment of IMR-32 cells with 40 pM CNTF produced a half-maximal decrease of alpha-bungarotoxin binding which compared well with the affinity estimated from binding of 125I-CNTF (Ki approximately 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 have indicated that the differentiating agents, phorbol esters and retinoic acid, also decrease nicotinic receptor numbers. Here the effects of CNTF, which did not induce neural differentiation, were enhanced by differentiation with 12-O-tetradecanoylphorbol 13-acetate (10 nM) and prevented by retinoic acid (10 microM). Therefore, the response of neuroblastoma cells to cytokines may be under developmental control. These cells offer a system to examine cytokine responses and signal transduction mechanisms during neural development.
Halvorsen
S W
SW
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York at Buffalo, NY 14260, USA.
Malek
R
R
Wang
X
X
Jiang
N
N
D002038:Bungarotoxins / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002038:Bungarotoxins; D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate