Azosemide is more potent than bumetanide and various other loop diuretics to inhibit the sodium-potassium-chloride-cotransporter human variants hNKCC1A and hNKCC1B.

ABSTRACT: The Na⁺-K⁺-2Cl^- cotransporter NKCC1 plays a role in neuronal Cl^- homeostasis secretion and represents a target for brain pathologies with altered NKCC1 function. Two main variants of NKCC1 have been identified: a full-length NKCC1 transcript (NKCC1A) and a shorter splice variant (NKCC1B) that is particularly enriched in the brain. The loop diuretic bumetanide is often used to inhibit NKCC1 in brain disorders, but only poorly crosses the blood-brain barrier. We determined the sensitivity of the two human NKCC1 splice variants to bumetanide and various other chemically diverse loop diuretics, using the Xenopus oocyte heterologous expression system. Azosemide was the most potent NKCC1 inhibitor (IC₅₀s 0.246 µM for hNKCC1A and 0.197 µM for

SUBMITTER: Hampel P 

PROVIDER: S-EPMC6026185 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature