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Role of Egr‐1 in Cholinergic Stimulation of Phenylethanolamine N ‐Methyltransferase Promoter
Author(s) -
Morita Kyoji,
Wong Dona L.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67041344.x
Subject(s) - carbachol , phenylethanolamine n methyltransferase , phenylethanolamine , cholinergic , endocrinology , chemistry , medicine , stimulation , microbiology and biotechnology , biology , tyrosine hydroxylase , dopamine
The effects of the cholinergic agonist carbachol on phenylethanolamine N ‐methyltransferase promoter activity and Egr‐1 mRNA expression in PC12‐derived RS1 cells were examined to investigate the potential involvement of Egr‐1 in the neural regulation of phenylethanolamine N ‐methyltransferase gene expression. Carbachol stimulated luciferase expression in cells transfected with a rat phenylethanolamine N ‐methyltransferase promoter‐luciferase reporter gene construct and also elevated Egr‐1 mRNA levels in untransfected cells. Maximum induction of Egr‐1 mRNA by carbachol was rapid (0.5 h), whereas by comparison, peak luciferase activity was delayed (6 h). In addition, carbachol stimulation of both luciferase and Egr‐1 mRNA expression could be completely inhibited by atropine but not hexamethonium. Furthermore, bethanechol but not nicotine could mimic the effects of carbachol, indicating that carbachol activation was medicated through muscarinic cholinergic receptors. Finally, carbachol failed to stimulate luciferase expression in cells transfected with a mutant construct, in which the Egr‐1 binding element in the phenylethanolamine N ‐methyltransferase promoter was mutated. These results suggest that carbachol activates the phenylethanolamine N ‐methyltransferase promoter through stimulation of Egr‐1 expression, and are consistent with the potential involvement of Egr‐1 in the cholinergic activation of the phenylethanolamine N ‐methyltransferase gene.