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Alpha1-adrenoceptors down-regulate ClC-2 chloride channels in epithelial cells from the acutely denervated jejunum
Carolyn J Baglole1, David L Sigalet, Jonathan B Meddings
1Gastrointestinal Research Group, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, Canada T2N 4N1. carolyn_baglole@urmc.rochester.edu
Abstract:
Acute sympathetic denervation of the small intestine up-regulates alpha1-adrenoceptors on villus enterocytes and activation of these alpha1-adrenoceptors inhibits chloride secretion. We tested whether alpha1-adrenoceptor-mediated inhibition of chloride secretion was the result of reduced ClC-2 chloride channel expression. Phorbol myristate acetate (PMA) (a protein kinase C (PKC) activator) had no effect on ClC-2 levels. In contrast, alpha1-adrenoceptor activation significantly decreased ClC-2 protein levels in both the villus (1.58+/-0.19 to 0.75+/-0.19 arbitrary units) and crypt (1.69+/-0.15 to 0.37+/-0.23 arbitrary units) epithelial cells from the acutely denervated jejunum but not innervated controls. These data suggest that inhibition of chloride secretion following alpha1-adrenoceptor activation in the acutely denervated small intestine may be through ClC-2 down-regulation.
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