Probenecid Pre-treatment Downregulates the Kidney Cl^-/HCO₃^- Exchanger (Pendrin) and Potentiates Hydrochlorothiazide-Induced Diuresis.

ABSTRACT: Background: Probenecid is a uricosuric agent that in addition to exerting a positive ionotropic effect in the heart, blocks the ATP transporter Pannexin 1 and inhibits the Cl^-/HCO₃^- exchanger, pendrin. In the kidney, pendrin blunts the loss of salt wasting secondary to the inhibition of the thiazide-sensitive Na⁺-Cl^- co-transporter (NCC/SLC12A3). Hypothesis: Pre-treatment with probenecid down-regulates pendrin; therefore, leaving NCC as the main salt absorbing transporter in the distal nephron, and hence enhances the hydrochlorothiazide (HCTZ)-induced diuresis. Methods: Daily balance studies, blood and urine chemical analysis, immunofluorescence, as well as western and northern blot analyses were utilized to examin

SUBMITTER: Barone S 

PROVIDER: S-EPMC6050369 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature