| Autor: |
Zhao, Aiping, Bossone, Carol, Piñeiro-Carrero, Victor, Shea-Donohue, Terez |
| Zdroj: |
The Journal of Pharmacology and Experimental Therapeutics; November 2001, Vol. 299 Issue: 2 p768-774, 7p |
| Abstrakt: |
The present study investigated inflammation-induced changes in adrenergic regulation of smooth muscle. Colitis was induced in rats by intrarectal administration of trinitrobenzenesulfonic acid in ethanol. After 4 h (acute) or 7 days (chronic), in vitro isometric tension was measured in strips of circular smooth muscle taken from the distal colon. In controls, the major inhibitory control of smooth muscle responses to nerve stimulation was mediated by nitric oxide and β adrenergic receptors. There was less evidence of α adrenergic control. Studies with the β3receptor antagonist cyanopindolol and the β3receptor agonist BRL37344 revealed that β adrenergic regulation of spontaneous contractions and responses to nerve stimulation were mediated primarily by the β3adrenoreceptor. Both acute and chronic colitis significantly increased responses to electrical field stimulation. This effect was attributed to a loss of inhibitory nitrergic regulation as well as to selective changes in the β adrenergic control of colonic circular smooth muscle. Inflammation did not alter α adrenergic control. Chronic colitis also decreased the sensitivity to nerve stimulation and pharmacological contractile agents. Acute and chronic inflammation reduced the ability of BRL37344 to inhibit contractions in response to nerve stimulation. In addition, in inflamed colon, BRL37344 was less effective in relaxing carbachol-induced precontractions. Finally, inflammation resulted in a loss of the ability of the cyanopindolol to increase the amplitude of both spontaneous contractions and contractions in response to nerve stimulation. These effects indicated that colitis induced a down-regulation of inhibitory β3adrenergic control of colonic smooth muscle function. This loss of adrenergic regulation may contribute to the diarrhea in inflammatory bowel disease. |
| Databáze: |
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