HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/G1020    most recent 00159.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by El-Yazbi, A. F. Articles by Daniel, E. E. Search for Related Content PubMed PubMed Citation Articles by El-Yazbi, A. F. Articles by Daniel, E. E.

MUCOSAL BIOLOGY

Caveolin-1 knockout alters -adrenoceptors function in mouse small intestine

Departments of ¹Pharmacology and ²Pediatrics, University of Alberta, Edmonton, Alberta, Canada

Submitted 13 April 2006 ; accepted in final form 11 June 2006

-Adrenoceptors are G protein-coupled receptors whose functions are closely associated with caveolae in the heart and cultured cell lines. In the gut, they are responsible, at least in part, for the mediation of the sympathetic stimulation that might lead to intestinal paralysis postoperatively. We examined the effect of caveolin-1 knockout on the -adrenoceptor response in mouse small intestine. The relaxation response to (–)-isoprenaline in carbachol-contracted small intestinal tissue segments was reduced in caveolin-1 knockout mice (cav1^–/–) compared with their genetic controls (cav1^+/+). Immunohistochemical staining showed that -adrenoceptor expression was similar in both strains in gut smooth muscle. Selective -adrenoceptor blockers shifted the concentration response curve (CRC) of (–)-isoprenaline to the right in cav1^+/+ intestine, but not in cav1^–/–, with greatest shift in case of the ₃-blocker, SR59230A. The CRC of the selective ₃-agonist BRL 37344 was also shifted to the right in cav1^–/– compared with cav1^+/+. The cAMP-dependent protein kinase (PKA) inhibitor H-89 shifted the CRC of (–)-isoprenaline to the right in cav1^+/+ but not in cav1^–/–. H-89 reduced the relaxation due to forskolin and dibutyryl cAMP in cav1^+/+ but not in cav1^–/–, suggesting a reduction in PKA activity in cav1^–/–. In cav1^+/+, PKA was colocalized with caveolin-1 in the cell membrane, but PKA immunoreactivity persisted in cav1^–/–. Examination of PKA expression in the lipid raft-rich membrane fraction of the jejunum revealed reduced PKA expression in cav1^–/– compared with cav1^+/+. The results of the present study show that the function of -adrenoceptors is reduced in cav1^–/– small intestine likely owing to reduced PKA activity.

protein kinase A; isoprenaline; forskolin; adenosine 3',5'cyclic-monophosphate

This article has been cited by other articles:

				M. Wuest, B. Eichhorn, M. O. Grimm, M. P. Wirth, U. Ravens, and A. J. Kaumann Catecholamines Relax Detrusor through {beta}2-Adrenoceptors in Mouse and {beta}3-Adrenoceptors in Man J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 213 - 222. [Abstract] [Full Text] [PDF]