Neural stimulation of Egr-1 messenger RNA expression in rat adrenal gland: possible relation to phenylethanolamine N-methyltransferase gene regulation.
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.
Morita
K
K
Nancy Pritzker Laboratory of Developmental and Molecular Neurobiology, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California, USA.
Bell
R A
RA
Siddall
B J
BJ
Wong
D L
DL
D000311:Adrenal Glands / Q000294:innervation / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D016762:Genes, fos; D017874:Immediate-Early Proteins; D008297:Male; D016716:PC12 Cells; D010433:Pentylenetetrazole / Q000494:pharmacology; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013153:Splanchnic Nerves / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D010625:Phenylethanolamine N-Methyltransferase; D010433:Pentylenetetrazole