This review summarizes the data on the functional significance of ubiquitous (NKCC1) and renal-specific (NKCC2) isoforms of electroneutral sodium, potassium and chloride cotransporters. These carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid, respectively. Both NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid volume. However, the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477834 | PMC |
| http://dx.doi.org/10.1016/j.gendis.2015.02.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inflammatory Pathways of Sulfonamide Diuretics: Insights into SLC12A Cl Symporters and Additional Targets.
Cell Physiol Biochem
January 2025
Department of Pharmacology and Toxicology, Wright State University, School of Medicine. Dayton, Ohio, United States,
Thiazide, thiazide-like, and loop diuretics are primarily known for inhibiting members of the SLC12A family of Cl transporters, which include the Na+Cl cotransporter (NCC), NaK2Cl cotransporters (NKCC1 and NKCC2) and KCl symporters (KCC1-4). While the main pharmacological effect of these diuretics is diuresis, achieved by promoting the excretion of excess water and salt through the kidneys, they have intriguing pharmacological effects beyond their traditional ones which cannot be solely attributed to their effects on renal salt transport. Of particular interest is their role in modulating inflammatory processes.
View Article and Find Full Text PDFPeripheral Blood Mononuclear Cell Expression of Cation-Chloride Cotransporter (CCC) Genes in Premenstrual Dysphoric Disorder (PMDD) across the Menstrual Cycle-A Preliminary Study.
Biology (Basel)
May 2024
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Article Synopsis
- PMDD is a psychiatric disorder affecting women during the luteal phase of their menstrual cycle, causing severe emotional symptoms.
- The study aimed to investigate how gene expression related to cation-chloride cotransporters (CCC) varies in women with PMDD, using peripheral blood mononuclear cells (PBMCs) as an alternative to directly studying the brain.
- Results indicated a significant downregulation of the KCC1 gene during specific menstrual phases in women with PMDD, supporting PBMCs as a useful model for understanding the GABA-related mechanisms involved in this condition.
The role of family of cation-chloride cotransporters and drug discovery methodologies.
J Pharm Anal
December 2023
Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 363001, China.
The () of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl loading.
View Article and Find Full Text PDFTranscriptional regulation of esophageal, intestinal, and branchial solute transporters by salinity, growth hormone, and cortisol in Atlantic salmon.
J Exp Zool A Ecol Integr Physiol
January 2024
Department of Biology, University of Massachusetts, Amherst, Massachusetts, USA.
Article Synopsis
- - Atlantic salmon need to drink seawater to maintain body hydration, and the esophagus helps by desalinating this water for absorption in the intestines.
- - The study focused on two Na/H exchangers (Nhe2 and Nhe3) in the esophagus and found that while Nhe3 expression increased after 48 hours in seawater, there were no changes during the seasonal smoltification process.
- - Cortisol plays a key role in enhancing the function of ion transporters in the esophagus and intestines, helping salmon adapt to seawater by modulating the expression of important genes involved in salt absorption.
Evaluation of bumetanide as a potential therapeutic agent for Alzheimer's disease.
Front Pharmacol
August 2023
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States.
Therapeutics discovery and development for Alzheimer's disease (AD) has been an area of intense research to alleviate memory loss and the underlying pathogenic processes. Recent drug discovery approaches have utilized computational strategies for drug candidate selection which has opened the door to repurposing drugs for AD. Computational analysis of gene expression signatures of patients stratified by the APOE4 risk allele of AD led to the discovery of the FDA-approved drug bumetanide as a top candidate agent that reverses APOE4 transcriptomic brain signatures and improves memory deficits in APOE4 animal models of AD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!