Neural stimulation of Egr-1 messenger RNA expression in rat adrenal gland: possible relation to phenylethanolamine N-methyltransferase gene regulation

K Morita, RA Bell, BJ Siddall and DL Wong

Nancy Pritzker Laboratory of Developmental and Molecular Neurobiology, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California, USA.

Metrazole, which reflexively activates the splanchnic nerve to the adrenal medulla, was used to investigate the physiological role of Egr- 1 in the neural regulation of phenylethanolamine N-methyltransferase (PNMT) gene transcription in the rat adrenal gland. A single dose of this drug (70 mg/kg s.c.) rapidly and transiently induced Egr-1 mRNA, with a maximum 22.0-fold increase at 30 min after treatment, followed by a 3.7-fold increase in PNMT mRNA at 8 hr. In contrast, cocaine (15 mg/kg i.p.), which activates the hypothalamic-pituitary-adrenal axis, increased Egr-1 mRNA only 3-fold at 30 min, although it elevated PNMT mRNA comparably. Consistent with their mechanisms of activation, cocaine increased corticosterone levels 7.7-fold at 30 min, whereas metrazole modestly elevated this endogenous corticosteroid 2.5-fold. The cholinergic agonists nicotine (2 mg/kg l.p.) and muscarine (0.1 mg/kg i.p.) also elevated Egr-1 mRNA, with a peak 12- to 15-fold increase being apparent at 30 min after treatment, followed by a 1.7-to 2.0-fold rise in PNMT mRNA at 8 hr. In vitro, metrazole did not increase Egr-1 mRNA above levels observed with carbachol alone (100 microM) in PC-12-derived RS1 cells pretreated with this cholinergic agonist. Finally, splanchnic denervation partially blocked the metrazole-induced rise in Egr-1 mRNA (50% control), while having no effect on cocaine-induced changes in Egr-1 mRNA. These results provide further support for the involvement of Egr-1 in the neural regulation of PNMT gene expression in the rat adrenal gland.

Volume 279, Issue 1, pp. 379-385, 10/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

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