Next Article in Journal
Multiplex Digital PCR to Detect Amplifications of Specific Androgen Receptor Loci in Cell-Free DNA for Prognosis of Metastatic Castration-Resistant Prostate Cancer
Next Article in Special Issue
Electroporation-Based Treatments in Urology
Previous Article in Journal
Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
Previous Article in Special Issue
Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a
Article

Cisplatin Decreases ENaC Activity Contributing to Renal Salt Wasting Syndrome

1
Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900, USA
2
Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(8), 2140; https://doi.org/10.3390/cancers12082140
Received: 30 June 2020 / Revised: 21 July 2020 / Accepted: 27 July 2020 / Published: 1 August 2020
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
Cisplatin (CDDP) is an important anticancer drug. A common side effect of CDDP is renal salt and water-wasting syndrome (RSWS). The origin of RSWS is obscure. Emerging evidence, though, suggests that broad inhibition of sodium transport proteins by CDDP may result in decreases in tubular reabsorption, causing increases in sodium and water excretion. In this sense, CDDP would be acting like a diuretic. The effect of CDDP on the epithelial Na+ channel (ENaC), which is the final arbiter fine-tuning renal Na+ excretion, is unknown. We test here whether CDDP affects ENaC to promote renal salt and water excretion. The effects of CDDP and benzamil (BZM), a blocker of ENaC, on excretion of a sodium load were quantified. Similar to BZM, CDDP facilitated renal Na+ excretion. To directly quantify the effects on ENaC, principal cells in split-open tubules were patch clamped. CDDP, at doses comparable to those used for chemotherapy (1.5 µM), significantly decreased ENaC activity in native tubules. To further elaborate on this mechanism, the dose-dependent effects of CDDP on mouse ENaC (mENaC) heterologously expressed in Chinese Hamster Ovary (CHO) cells were tested using patch clamping. As in native tubules, CDDP significantly decreased the activity of mENaC expressed in CHO cells. Dose–response curves and competition with amiloride identified CDDP as a weak inhibitor of ENaC (apparent IC50 = 1 µM) that competes with amiloride for inhibition of the channel, weakening the inhibitory actions of the latter. Such observations are consistent with CDDP being a partial modulator of ENaC, which possibly has a binding site that overlaps with that of amiloride. These findings are consistent with inhibition of ENaC by CDDP contributing to the RSWS caused by this important chemotherapy drug. View Full-Text
Keywords: Deg/ENaC channels; renal sodium excretion; hypertension; diuretic; pseduohypoaldosteronism; chemotherapy Deg/ENaC channels; renal sodium excretion; hypertension; diuretic; pseduohypoaldosteronism; chemotherapy
Show Figures

Figure 1

MDPI and ACS Style

Soares, A.G.; Mironova, E.; Archer, C.R.; Contreras, J.; Stockand, J.D.; Abd El-Aziz, T.M. Cisplatin Decreases ENaC Activity Contributing to Renal Salt Wasting Syndrome. Cancers 2020, 12, 2140. https://doi.org/10.3390/cancers12082140

AMA Style

Soares AG, Mironova E, Archer CR, Contreras J, Stockand JD, Abd El-Aziz TM. Cisplatin Decreases ENaC Activity Contributing to Renal Salt Wasting Syndrome. Cancers. 2020; 12(8):2140. https://doi.org/10.3390/cancers12082140

Chicago/Turabian Style

Soares, Antonio G., Elena Mironova, Crystal R. Archer, Jorge Contreras, James D. Stockand, and Tarek M. Abd El-Aziz 2020. "Cisplatin Decreases ENaC Activity Contributing to Renal Salt Wasting Syndrome" Cancers 12, no. 8: 2140. https://doi.org/10.3390/cancers12082140

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop