Gentamicin Inhibits Ca²⁺ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor-Claudin-14 Pathway.

ABSTRACT:

Background

Treatment with the aminoglycoside antibiotic gentamicin can be associated with severe adverse effects, including renal Ca²⁺ wasting. The underlying mechanism is unknown but it has been proposed to involve activation of the Ca²⁺-sensing receptor (CaSR) in the thick ascending limb, which would increase expression of claudin-14 (CLDN14) and limit Ca²⁺ reabsorption. However, no direct evidence for this hypothesis has been presented.

Methods

We studied the effect of gentamicin in vivo using mouse models with impaired Ca²⁺ reabsorption in the proximal tubule and the thick ascending limb. We used a Cldn14 promoter luciferase reporter assay to study CaSR activation and investigated the effect of gentamicin on activ

SUBMITTER: van Megen WH 

PROVIDER: S-EPMC8975070 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature