Mirabegron Relaxes Urethral Smooth Muscle By A Dual Mechanism Involving β3 -adrenoceptor Activation And α1 -adrenoceptor Blockade.

dc.creatorAlexandre, E C
dc.creatorKiguti, L R
dc.creatorCalmasini, F B
dc.creatorSilva, F H
dc.creatorda Silva, K P
dc.creatorFerreira, R
dc.creatorRibeiro, C A
dc.creatorMónica, F Z
dc.creatorPupo, A S
dc.creatorAntunes, E
dc.date2016-Feb
dc.date2016-05-23T19:39:44Z
dc.date2016-05-23T19:39:44Z
dc.date.accessioned2018-03-29T01:27:23Z
dc.date.available2018-03-29T01:27:23Z
dc.identifierBritish Journal Of Pharmacology. v. 173, n. 3, p. 415-428, 2016-Feb.
dc.identifier1476-5381
dc.identifier10.1111/bph.13367
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/26493129
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/235123
dc.identifier26493129
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1303366
dc.descriptionThis article is commented on by Michel, M. C., pp. 429-430 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.13379. Mirabegron is the first β3 -adrenoceptor agonist approved for treatment of overactive bladder syndrome. This study aimed to investigate the effects of β3 -adrenoceptor agonist mirabegron in mouse urethra. The possibility that mirabegron also exerts α1 -adrenoceptor antagonism was also tested in rat smooth muscle preparations presenting α1A - (vas deferens and prostate), α1D - (aorta) and α1B -adrenoceptors (spleen). Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]prazosin to membrane preparations of HEK-293 cells expressing each of the human α1 -adrenoceptors, as well as β-adrenoceptor mRNA expression and cyclic AMP measurements in mouse urethra, were performed. Mirabegron produced concentration-dependent urethral relaxations that were shifted to the right by the selective β3 -adrenoceptor antagonist L-748,337 but unaffected by β1 - and β2 -adrenoceptor antagonists (atenolol and ICI-118,551 respectively). Mirabegron-induced relaxations were enhanced by the PDE4 inhibitor rolipram, and the agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1 -adrenoceptor agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1 -adrenoceptors in urethra, vas deferens and prostate (α1A -adrenoceptor, pA2  ≅ 5.6) and aorta (α1D -adrenoceptor, pA2  ≅ 5.4) but not in spleen (α1B -adrenoceptor). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A - and α1D -adrenoceptors (pKi  ≅ 6.0). The effects of mirabegron in urethral smooth muscle are the result of β3 -adrenoceptor agonism together with α1A and α1D -adrenoceptor antagonism.
dc.description173
dc.description415-428
dc.languageeng
dc.relationBritish Journal Of Pharmacology
dc.relationBr. J. Pharmacol.
dc.rightsfechado
dc.sourcePubMed
dc.titleMirabegron Relaxes Urethral Smooth Muscle By A Dual Mechanism Involving β3 -adrenoceptor Activation And α1 -adrenoceptor Blockade.
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución