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Caveolin‐1 knockout alters β‐adrenoceptor (β‐AR) function in mouse small intestine
Author(s) -
ElYazbi Ahmed Fawzy,
Schulz Richard,
Daniel Edwin
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a248-b
Subject(s) - caveolae , endocrinology , knockout mouse , medicine , agonist , receptor , caveolin 1 , isoprenaline , chemistry , small intestine , carbachol , caveolin 3 , biology , microbiology and biotechnology , signal transduction , stimulation
β‐ARs transduce signals intracellularly via G‐proteins. β 2 ‐ARs localize in caveolae and co‐immunoprecipitate with caveolin‐3 in cardiac myocytes. Cholesterol depletion disrupts caveolae and alters both β 2 ‐AR function and localization, suggesting that caveolins regulate these receptors. β‐AR activation in mouse small intestine relaxes smooth muscle, mainly via β3, but also via β1 and β 2 ‐ARs. Here we examined the effects of caveolin‐1 (cav1) knockout on β‐AR function in mouse small intestine in vitro . In tissue segments contracted with carbachol, isoprenaline (iPr) induced relaxation. The iPr dose‐effect (D‐E) curve in the cav1 knockout (cav1 ‐/‐ ) mice was shifted to the right compared to wild type controls. In control mice, SR 59230A (β3‐blocker) and timolol (β 1 /β 2 ‐blocker) showed similar rightward shifts in the iPr D‐E curve that were greater compared to CGP20712A (β 1 ‐blocker). In intestine of cav1 ‐ / ‐ , SR 59230A and CGP 20712A were without effect; only timolol significantly shifted the D‐E curve. BRL 37344 (β 3 ‐agonist) was more effective in controls than in cav1 ‐/‐ intestine, but salbutamol (β 2 ‐agonist) relaxed both similarly. Dibutyryl cAMP relaxed intestine in control mice‐ this was prevented by H‐89 (PKA inhibitor). In cav1 ‐/‐ , H‐89 had no effect on relaxation. These results suggest that cav1 knockout reduces β 3 (and perhaps β 1 ) receptor function in the small intestine. β 2 ‐ARs may partially compensate for this loss. Reduced PKA responses may explain these results. Functional and immunohistochemical experiments are underway to elucidate the interaction between the different β‐receptor subtypes and cav1. Supported by CIHR.