Autor(es)

Passos, Gabriela Reolon ; Antunes, Natalicia de Jesus ; de Oliveira, Mariana G. ; da Costa, Jose Luiz ; Schenka, Andre Almeida ; Fregonesi, Adriano ; Antunes, Edson ; Monica, Fabiola Zakia

• Tipo de documento: Artigo Científico
• Fonte: World Journal of Urology; v. 43, n. 1, p. 11-pg., 2025-09-09.

Resumo

PurposeTo evaluate the impact of MRP inhibition by MK571 on prostate hypercontractility in diet-induced obesity, based on the hypothesis that this intervention enhances intracellular cAMP and cGMP signaling.MethodsAdult C57BL/6 mice were divided into three groups: (i) lean, (ii) obese, and (iii) obese + MK571 (5 mg/kg/day, 14 days). The prostate was isolated for immunohistochemistry, biochemistry and functional assays. Electrical field stimulation (EFS) and concentration-response curves to the alpha 1-adrenoceptor agonist phenylephrine or the nitric oxide donor sodium nitroprusside were performed with or without MK571 (20 mu M, 30 min), guanylyl or adenylyl cyclase inhibitors (ODQ and SQ22,536, respectively), or the leukotriene receptor antagonist montelukast.ResultsMRP4 and MRP5 were detected in the prostate. In vitro, phenylephrine-and EFS-induced contractions were significantly higher in prostates from obese mice compared to lean mice. Adding MK571 to the myograph chamber significantly reduced the contractile responses and improved relaxation in obese mice, reaching similar responses to those of the lean group. These effects of MK571 were inhibited by co-incubation with ODQ and SQ22536, but not by montelukast. Additionally, treating obese mice for 14 days reversed prostate hypercontractility. Obese mice exhibited significantly lower intracellular levels of cGMP compared to lean, while cAMP levels were similar. However, MK571 treatment significantly increased both cyclic nucleotides, restoring cGMP levels close to those in lean mice.ConclusionOur findings highlight that inhibiting MRPs promotes the accumulation of cGMP in the prostate, ultimately enhancing smooth muscle relaxation. (AU)

• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 24/03517-9 - Caracterização farmacológica da probenecida em órgãos isolados do trato geniturinário inferior e em modelos de disfunção erétil e miccional: possível reposicionamento da probenecida?
• Beneficiário: Fabíola Taufic Monica Iglesias
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/11621-5 - Avaliação do efeito das espécies reativas de oxigênio na viabilidade de linhagens de células prostáticas epiteliais e estromais e na reatividade de fragmentos oriundos de próstata de pacientes submetidos a ressecção prostática.
• Beneficiário: Gabriela Reolon Passos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado