Abstract
Functional involvement of beta3-adrenoceptors in controlling human gastrointestinal motility has not been unequivocally assessed yet. The direct myogenic contribution of these receptors was examined, by in vitro functional studies and analysis of mRNA expression, on smooth muscle cells separately isolated from taenia coli and circular muscle layers of the human colon. Isoproterenol, a nonselective beta-adrenoceptor agonist, relaxed, in a concentration-dependent manner, both human taenia coli and circular colonic smooth muscle cells, although displaying a higher intrinsic activity (65.3 +/- 2.3 vs. 55.2 +/- 1.4% maximal relaxation) and potency (pEC50: 7.41 +/- 0.07 vs. 6.32 +/- 0.08) were greater on taenia coli than circular cells. In the presence of the beta1-antagonist CGP20712A and of the beta2-antagonist ICI 118,551, a 25-30% decrease in isoproterenol intrinsic activity was observed on both cell types and on taenia coli, the nonselective beta1/beta2-antagonist propranolol produced a rightward shift of the isoproterenol concentration-response curve with mean estimated pKB values (8.12 +/- 0.27 at 0.1 microM and 6.45 +/- 0.13 at 1 microM) lower than that expected for both beta1- and beta2-adrenoceptors. CGP12177A and SR 58611A...Continue Reading
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