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• W1964513650 abstract "In this study, responses of β3-adrenoceptor agonists were examined on human isolated internal anal sphincter (IAS) in order to explore their relaxant effects on hypertonicity of IAS. The relaxant efficacy (Emax) and potency (− logIC50) of BRL37344 and SR58611A, β3-adrenoceptor agonists, were examined in contracted IAS muscle strips. The presence of β3-adrenoceptors, and changes in intracellular calcium and cyclic nucleotide levels in IAS muscle were tested by Western blotting, epifluorescence microscopy and enzyme immunoassay, respectively. BRL37344 and SR58611A relaxed contracted IAS muscle (Emax = 27 ± 3% and 35 ± 3%; -logIC50 = 6.26 ± 0.24 and 4.87 ± 0.13; respectively). These relaxant responses were blocked by SR59230A, a selective β3-antagonist but not by β1/β2-selective antagonists, neuronal inhibitor or inhibition of nitric oxide synthase. The Emax of β3-agonists was similar to that of β2-selective agonists but smaller than that of isoprenaline (nonselective agonist) or β1-selective agonists. BRL37344 (100 μM) increased cAMP (1.5-fold) without cGMP change, and depressed intracellular calcium signal. β3-Adrenoceptor expression was smaller than that of β1- and β2-adrenoceptors. This is the first study demonstrating the presence of β3-adrenoceptor in human IAS muscle and β3-mediated relaxation of augmented sphincter tone. However, direct β3-relaxation appears smaller than that obtained for nonselective agonists which may limit their potential use in the treatment of anorectal hypertonicity disorders." @default.
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• W1964513650 date "2010-02-01" @default.
• W1964513650 modified "2023-09-25" @default.
• W1964513650 title "Relaxation by β3-adrenoceptor agonists of the isolated human internal anal sphincter" @default.
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• W1964513650 doi "https://doi.org/10.1016/j.lfs.2010.01.005" @default.
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