Artículos de revistas
Soluble Guanylate Cyclase Modulators, Bay 41-2272 And Bay 60-2770, Inhibit Human And Rabbit Prostate Contractility
Registro en:
Urology. Elsevier Science Inc, v. 94, p. 312 - U392, 2016.
0090-4295
1527-9995
WOS:000383696400071
10.1016/j.urology.2016.04.023
Autor
Calmasini
Fabiano B.; Alexandre
Eduardo C.; Silva
Fabio Henrique; De Nucci
Gilberto; Antunes
Edson; D'Ancona
Carlos A.; Monica
Fabiola Z.
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) To 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. 94 312 U392 Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/13907-4, 2014/02195-6] Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)