Regulation of α3 Nicotinic Acetylcholine Receptor Subunit mRNA Levels by Nerve Growth Factor and Cyclic AMP in PC12 Cells

• Published in: Journal of neurochemistry Vol. 74; no. 4; pp. 1346 - 1354
• Main Authors: Nakayama, Hitoshi, Ueno, Satoshi, Ikeuchi, Toshihiko, Hatanaka, Hiroshi
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.04.2000; Blackwell
• Subjects: Acetylcholine receptor; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cyclic AMP; Fundamental and applied biological sciences. Psychology; Nerve growth factor; Nicotinic receptor; PC12 cells; Regulation; Vertebrates: nervous system and sense organs; Signal transduction; Cholinergic receptor; Regulation(control); Cell line; Neuron; Cyclic AMP; Nerve growth factor; Gene expression; Subunit; In vitro; Nicotinic receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0741346.x

: To investigate the effects of nerve growth factor (NGF) and cyclic AMP (cAMP) on the level of the nicotinic acetylcholine receptor subunit α3 mRNA, we used PC12h cells, PC12 cells expressing dominant‐negative Ras protein, and the parental PC12 cells. PC12h cells have NGF‐responsive tyrosine hydroxylase activity. Expression of dominant‐negative Ras protein prevents the signaling through the Ras‐mitogen‐activated protein kinase cascade. The morphological changes of the parental PC12 cells in response to NGF and 8‐(4‐chlorophenylthio)adenosine 3′,5′‐cyclic monophosphate (CPTcAMP), a cell‐penetrating cAMP analogue, were similar to those of PC12h cells. NGF up‐regulated the α3 mRNA level in PC12h cells and down‐regulated the α3 mRNA level in the parental PC12 cells. Expression of dominant‐negative Ras protein and an inhibitor of mitogen‐activated protein kinase kinase inhibited the effects of NGF on α3 mRNA level. CPTcAMP down‐regulated the α3 mRNA level in all three PC12 cell lines. An inhibitor of protein kinase A inhibited the CPTcAMP‐induced down‐regulation of α3 mRNA. The α3 mRNA down‐regulation required prolonged treatment with CPTcAMP even after cAMP response element binding protein phosphorylation was decreased. Membrane depolarization with high K+ had no effect on the α3 mRNA level in PC12h cells. Based on these results, we propose that at least two unknown effectors regulate α3 mRNA levels in PC12 cells.