Regulation of tyrosine hydroxylase gene expression by muscarinic agonists in rat adrenal medulla.
Tyrosine hydroxylase (TH) gene expression in the adrenal medulla is regulated by numerous stimuli via transsynaptic mechanisms. The adrenal chromaffin cell receptors that mediate this transsynaptic response remain unidentified. In this report we demonstrate that the muscarinic acetylcholine receptor agonist bethanechol stimulates the TH gene transcription rate in both innervated and denervated adrenal glands. Hence, this muscarinic response is not dependent on transsynaptic influences, suggesting that agonist occupation of adrenal chromaffin cell muscarinic receptors is sufficient to activate intracellular signaling pathways that stimulate the TH gene. When bethanechol is administered repeatedly over a 3-h interval (four injections spaced 1 h apart), TH mRNA levels are increased two- to threefold at 6 and 12 h after the initial injection of drug. It is surprising that this induction of TH mRNA does not lead to increases in TH activity or TH protein level. These results are consistent with the hypothesis that both transcriptional and posttranscriptional mechanisms must be regulated to induce TH protein and that muscarinic agonists activate only a subset of these mechanisms.
Piech-Dumas
K M
KM
Department of Pharmacology and Physiology, University of Rochester Medical Center, New York 14642, USA.
Sterling
C R
CR
Tank
A W
AW
D000313:Adrenal Medulla / Q000201:enzymology* / Q000294:innervation; D000818:Animals; D018723:Bethanechol / Q000008:administration & dosage / Q000494:pharmacology; D003714:Denervation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D018721:Muscarinic Agonists; D012333:RNA, Messenger; D018723:Bethanechol; D014446:Tyrosine 3-Monooxygenase