Adrenocorticotropic hormone activation of adenylate cyclase in raphe neurons: multiple regulatory pathways control serotonergic neuronal differentiation

Journal of Neurobiology
M J Eaton, S R Whittemore

Abstract

The RN46A cell line was derived from embryonic day 13 rat medullary raphe cells by infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T antigen (tsT-ag). The RN46A cell line is neuronally restricted and constitutively differentiates following a shift to nonpermissive temperature. Differentiated RN46A cells express low levels of tryptophan hydroxylase (TPH) but no detectable levels of serotonin (5-HT). Treatment of cultures with the adrenocorticotropic hormone peptide ACTH4-10 up-regulates the expression of TPH immunoreactivity in differentiated RN46A cells, but 5-HT synthesis requires initial treatment with ACTH4-10, followed by partial membrane depolarizing conditions. Up-regulation of TPH by ACTH4-10 is apparently due to activation of adenylate cyclase, whereas the increased 5-HT synthesis with membrane depolarization can be blocked with the voltage-sensitive Ca(2+)-channel blockers nifedipine and omega-conotoxin. ACTH4-10 treatment also markedly up-regulates the expression of the 5-HT reuptake transporter, as do dibutyryl cyclic AMP and forskolin; chronic membrane depolarization has no effect on 5-HT reuptake. The expression of the high-affinity 5-HT1A receptor is increased threefold by ACTH4...Continue Reading

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Citations

Sep 6, 2000·Journal of Neuroscience Research·P L AndersenD J Schreyer
Feb 1, 1996·Molecular Neurobiology·S R Whittemore, E Y Snyder
Oct 15, 1998·Journal of Molecular Neuroscience : MN·S M Mockus, K E Vrana
Jul 17, 2003·Journal of Neuroscience Methods·Cynthia L BetheaScott R Whittemore
May 31, 2011·Molecular Brain·Paul R AlbertAnne M Millar
Jun 30, 2012·Pain Research and Treatment·Mary J EatonEva Widerström-Noga
Apr 28, 2006·American Journal of Human Genetics·Xian-Zhang HuDavid Goldman
Jul 25, 2000·Journal of the Peripheral Nervous System : JPNS·M J Eaton
Nov 28, 2020·Biochemical Pharmacology·Carmen M DeveauBryan K Yamamoto

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