# PubMed- Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function.



## VSsupport (Feb 12, 2008)

[TD]Related Articles

*Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function.*

Am J Physiol Gastrointest Liver Physiol. 2009 Apr 9;

Authors: Choudhury BK, Shi XZ, Sarna SK

Chronic stress precipitates or exacerbates the symptoms of functional bowel disorders, including motility dysfunction. The cellular mechanisms of these effects are not understood. We tested the hypothesis that heterotypic chronic stress (HeCS) elevates the release of norepinephrine from the adrenal medulla, which enhances transcription of the gene regulating expression of Cav1.2 (L-type) channels in colonic circular smooth muscle cells, resulting in enhanced colonic motor function. The experiments were performed in rats using a nine-day heterotypic chronic stress protocol. We found that HeCS, but not acute stress, time-dependently enhances the contractile response to acetylcholine in colonic circular smooth muscle strips and in single dissociated smooth muscle cells, the plasma levels of norepinephrine and the mRNA and protein expressions of the alpha1C subunit of Cav1.2 channels. These effects result in faster colonic transit and increase in defecation rate. The effects of HeCS are blocked by adrenalectomy, but not by depletion of norepinephrine in the sympathetic neurons. The inhibition of receptors for glucocortocoids, corticotropin-releasing hormone or nicotine also does not block the effects of heterotypic chronic stress. Norepinephrine acts on alpha- and beta3-adrenergic receptors to induce the transcription of alpha1C subunit. We conclude that HeCS alters colonic motor function by elevating the plasma levels of norepinephrine. Colonic motor dysfunction is associated with enhanced gene transcription of Cav1.2 channels in circular smooth muscle cells. These findings suggest the potential cellular mechanisms by which heterotypic chronic stress may exacerbate motility dysfunction in irritable bowel syndrome patients. Key words: Corticotropin-releasing hormone, corticosterone, enteric neurotransmitters, smooth muscle.

PMID: 19359422 [PubMed - as supplied by publisher]

View the full article


----------

