Soluble Guanylate Cyclase Modulators, Bay 41-2272 And Bay 60-2770, Inhibit Human And Rabbit Prostate Contractility

dc.creatorCalmasini
dc.creatorFabiano B.; Alexandre
dc.creatorEduardo C.; Silva
dc.creatorFabio Henrique; De Nucci
dc.creatorGilberto; Antunes
dc.creatorEdson; D'Ancona
dc.creatorCarlos A.; Monica
dc.creatorFabiola Z.
dc.date2016
dc.dateagos
dc.date2017-11-13T11:34:59Z
dc.date2017-11-13T11:34:59Z
dc.date.accessioned2018-03-29T05:49:06Z
dc.date.available2018-03-29T05:49:06Z
dc.identifierUrology. Elsevier Science Inc, v. 94, p. 312 - U392, 2016.
dc.identifier0090-4295
dc.identifier1527-9995
dc.identifierWOS:000383696400071
dc.identifier10.1016/j.urology.2016.04.023
dc.identifierhttp://www-sciencedirect-com.ez88.periodicos.capes.gov.br/science/article/pii/S0090429516301200
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/326525
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1363531
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionTo evaluate the inhibitory effect of soluble guanylate cyclase (sGC) stimulator, BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b] pyridine-3-yl] pyrimidin-4-ylamine) or activator, BAY 60-2770 (4-({(4-carboxybutyl) [ 2-(5-fluoro-2-{[ 40-(trifluoromethyl) biphenyl-4-yl] methoxy} phenyl) ethyl] amino} methyl) benzoic acid), in human and rabbit prostate smooth muscle contractility. MATERIALS AND METHODS In rabbit or human prostate, contractions induced by electrical field stimulation or phenylephrine (PE) were carried out in the presence of sGC stimulator, BAY 41-2272, or sGC activator, BAY 60-2770. The potency (pEC(50)) and maximal response (E-max) values were determined. Immunohistochemistry analysis for sGC alpha 1-subunit and quantification of intracellular levels of cyclic guanosine monophosphate (cGMP) were also performed. RESULTS In rabbit prostate, BAY 60-2770 (30 and 300 nM) inhibited the contractions induced by PE and electrical field stimulation. The coincubation with sGC inhibitor, ODQ, produced greater inhibitions on PE-induced contractions in comparison with BAY 60-2770 alone, mainly due to greater cGMP accumulation (70-and 5.7-fold, respectively). BAY 41-2272 (300 nM) increased and decreased, respectively, cGMP levels and PE-induced contractions, but in the presence of ODQ these effects were reversed. In human prostate, immunohistochemistry analysis revealed the presence of sGC a1-subunit on the transition zone. BAY 60-2770 (300 nM) reduced significantly Emax induced by PE in human prostate. CONCLUSION sGC activator seems to be a promising alternative to treat benign prostatic hyperplasia because it increases cGMP levels even when sGC is oxidized. (C) 2016 Elsevier Inc.
dc.description94
dc.description312
dc.descriptionU392
dc.descriptionFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/13907-4, 2014/02195-6]
dc.descriptionCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageEnglish
dc.publisherElsevier Science INC
dc.publisherNew York
dc.relationUrology
dc.rightsfechado
dc.sourceWOS
dc.titleSoluble Guanylate Cyclase Modulators, Bay 41-2272 And Bay 60-2770, Inhibit Human And Rabbit Prostate Contractility
dc.typeArtículos de revistas


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