Relaxation by β3-adrenoceptor agonists of the isolated human internal anal sphincter

Abstract Aims In this study, responses of β 3 -adrenoceptor agonists were examined on human isolated internal anal sphincter (IAS) in order to explore their relaxant effects on hypertonicity of IAS. Main methods The relaxant efficacy ( E max ) and potency (− logIC 50 ) of 50  = 6.26 ± 0.24 and 4.87 ± 0.13; respectively). These relaxant responses were blocked by SR59230A, a selective β 3 -antagonist but not by β 1 /β 2 -selective antagonists, neuronal inhibitor or inhibition of nitric oxide synthase. The E max of β 3 -agonists was similar to that of β 2 -selective agonists but smaller than that of isoprenaline (nonselective agonist) or β 1 -selective agonists. BRL37344 (100 μM) increased cAMP (1.5-fold) without cGMP change, and depressed intracellular calcium signal. β 3 -Adrenoceptor expression was smaller than that of β 1 - and β 2 -adrenoceptors. Significance This is the first study demonstrating the presence of β 3 -adrenoceptor in human IAS muscle and β 3 -mediated relaxation of augmented sphincter tone. However, direct β 3 -relaxation appears smaller than that obtained for nonselective agonists which may limit their potential use in the treatment of anorectal hypertonicity disorders.