Role of efflux transporters of cGMP and cAMP in the viability of normal and benign prostatic hyperplasia cells

• Grant number: 21/12696-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2021
• End date: June 30, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Fabíola Taufic Monica Iglesias
• Grantee: Marcela Blasi Machado de Moraes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate, AP.TEM

Abstract

In the cell membranes, there are specific transporters that promote the pump of the cyclic nucleotides out of the cell. These transporters are also key proteins that control the intracellular levels of these nucleotides. These transporters (also known as multidrug resistance proteins) include the subtypes MRP4 and MRP5, which are encoded by the genes Abcc4 and Abcc5, respectively. Our group has been showing in the prostate, urethra, and bladder from mice that the non-selective blocker of MRP4 and MRP5, MK 571 potentiated the relaxations induced by cAMP (bladder)- and cGMP (prostate and urethra)-augmenting substances. Yet, in the prostate from obese mice and from patients who underwent prostatectomy the expression of MRP5 or MRP4 was increased. MK 571 reduced significantly the contraction induced by phenylephrine. Therefore, we postulate that MRP4 and MRP5 have a key role in the regulation of lower urinary tract smooth muscle reactivity and, possibly, in cell proliferation. Regarding the latter hypothesis, there are several studies showing that in cancer cells lines, MRP4 is overexpressed, thus leading to greater cAMP or cGMP extrusion and cell proliferation. To test this hypothesis this project is aimed to evaluate the role of MK571 alone or co-incubated with substances that increase the intracellular levels of cGMP (BAY 41-2272, BAY 58-2667, tadalafil) and cAMP (forskolin and rolipram) in the viability of normal (PNT-1 and WPMY-1) and in human benign prostatic hyperplasia (BPH-1) cells. (AU)