A single transmitter regulates gene expression through two separate mechanisms: cholinergic regulation of phenylethanolamine N- methyltransferase mRNA via nicotinic and muscarinic pathways

  title={A single transmitter regulates gene expression through two separate mechanisms: cholinergic regulation of phenylethanolamine N- methyltransferase mRNA via nicotinic and muscarinic pathways},
  author={Marian J. Evinger and Paul R Ernsberger and Soundar Regunathan and Tong Hyub Joh and Donald J. Reis},
  booktitle={Journal of Neuroscience},
ACh regulates the gene encoding phenylethanolamine N-methyltransferase (PNMT) in bovine adrenal chromaffin cells. In addition to stimulating catecholamine release from these cells, cholinergic agents elevate transcription of the PNMT gene. Carbachol, which activates both nicotinic and muscarinic receptors, produces 12–19-fold increases in PNMT mRNA and a 22-fold increase in epinephrine release. Selective nicotinic and muscarinic antagonists (hexamethonium and atropine) each partially reduce… 

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Pituitary adenylate cyclase activating polypeptide (PACAP) regulates expression of catecholamine biosynthetic enzyme genes in bovine adrenal chromaffin cells

Although PACAP is an effective regulator for expression of all three catecholamine enzyme genes, its mechanism of action on PNMT mRNA appears to be distinctive from its effects on TH and DBH gene transcription.

Neural regulation of phenylethanolamine N-methyltransferase (PNMT) gene expression in bovine chromaffin cells differs from other catecholamine enzyme genes

Electrophoretic mobility shift assays with oligonucleotides encoding these regions of the PNMT promoter revealed distinctions in migration of nuclear protein complexes formed following treatment of chromaffin cells with nicotine, muscarine, or 50 mM K+.

Cholinergic and Peptidergic Regulation of Phenylethanolamine N‐Methyltransferase Gene Expression

Although PACAP stimulates rapid changes in transcription factor expression and PNMT promoter activity, its effects are long lasting, and the magnitude of stimulation and antagonist blockade with H‐89 or the polypeptide inhibitor PKI suggests that the extent of activation is much less than that with PACAP.

Expression of catecholamine-synthesizing enzymes, peptidylglycine α-amidating monooxygenase, and neuropeptide Y mRNA in the rat adrenal medulla after acute systemic nicotine

Results suggest that common transcriptional activation mechanisms may upregulate both catecholamine and neuropeptide synthesis in the adrenal medulla after nicotinic stimulation.

Regulation of Phenylethanolamine N‐Methyltransferase Gene Expression by Imidazoline Receptors in Adrenal Chromaffin Cells

This study evaluates the ability of clonidine and related drugs to regulate expression of the gene for the epinephrine‐synthesizing enzyme phenylethanolamine N‐methyltransferase (PNMT) in the rat adrenal gland and in bovine adrenal chromaffin cell cultures to link imidazoline receptors to neurotransmitter gene expression.

Nicotine stimulates expression of the PNMT gene through a novel promoter sequence

Nicotinic cholinergic stimuli appear to regulate expression of the epinephrinesynthesizing gene PNMT through a previously uncharacterized regulatory element.

Muscarinic excitation–secretion coupling in chromaffin cells

A unified picture is presented of the mechanisms of muscarinic excitation–secretion coupling in chromaffin cells that might contribute to the fine tuning of the catecholamine secretory response upon graded preganglionic stimulation and prolonged periods of time.



Cholinergic Stimulation of Inositol Phosphate Formation in Bovine Adrenal Chromaffin Cells: Distinct Nicotinic and Muscarinic Mechanisms

Cholinergic stimulation of bovine adrenal chromaffin cells results in the activation of phospholipase C by distinct muscarinic and nicotinic mechanisms.

Clonidine-displacing substance from bovine brain binds to imidazoline receptors and releases catecholamines in adrenal chromaffin cells.

It is concluded that endogenous CDS, prepared from brain, regulates the secretion of catecholamines from adrenal chromaffin cells, probably by activating imidazole receptors.

Stimulation of Formation of Inositol Phosphates in Primary Cultures of Bovine Adrenal Chromaffin Cells by Angiotensin II, Histamine, Bradykinin, and Carbachol

It is shown that histamine, bradykinin, and angiotensin II stimulate release of catecholamines from adrenal medulla using bovine adrenal chromaffin cells in culture, and these agonists as well as carbachol stimulate production of inositol phosphates.

Stimulation of neuronal acetylcholine receptors induces rapid gene transcription.

It is suggested that neurotransmitters may rapidly activate specific gene transcription in nondividing neuronally differentiated cells and a functional role for neurotransmitter induction of c-fos and actin expression in the nervous system is suggested.

Cholinoceptor regulation of cyclic AMP levels in bovine adrenal medullary cells

The results indicate that nicotinic cholinoceptors can increase cyclic AMP production in chromaffin cells by a mechanism that does not directly involve Gs, that is dependent on extracellular Ca2+ and that is sensitive to the calmodulin antagonists W7 and trifluoperazine.

Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: partial amino acid homology with rat tyrosine hydroxylase.

  • E. BaetgeY. SuhT. Joh
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1986
Comparison of the deduced amino acid sequence of bovine PNMTase to rat tyrosine hydroxylase reveals that PnMTase shares significant homology with tyrosin hydroxyase and supports previous protein and immunological data suggesting that the catecholamine biosynthetic enzymes are structurally related.