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


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Article Info

DATE

2018-06-29

AUTHORS

Philip Hampel, Kerstin Römermann, Nanna MacAulay, Wolfgang Löscher

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 NKCC1B), being about 4-times more potent than bumetanide. Structurally, a carboxylic group as in bumetanide was not a prerequisite for potent NKCC1 inhibition, whereas loop diuretics without a sulfonamide group were less potent. None of the drugs tested were selective for hNKCC1B vs. hNKCC1A, indicating that loop diuretics are not a useful starting point to design NKCC1B-specific compounds. Azosemide was found to exert an unexpectedly potent inhibitory effect and as a non-acidic compound, it is more likely to cross the blood-brain barrier than bumetanide. More... »

PAGES

9877

References to SciGraph publications

  • 2001-07-06. Expression and role of sodium, potassium, chloride cotransport (NKCC1) in mouse inner medullary collecting duct (mIMCD-K2) epithelial cells in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1983-03. Effect of “high ceiling” diuretics on active salt transport in the cortical thick ascending limb of Henle's loop of rabbit kidney in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 2013-10-06. Physiology and pathophysiology of SLC12A1/2 transporters in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1986-12. Torasemide inhibits NaCl reabsorption in the thick ascending limb of the loop of Henle in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 2002-02-01. Rat NKCC2/NKCC1 cotransporter selectivity for loop diuretic drugs in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2009-12-15. Differential water permeability and regulation of three aquaporin 4 isoforms in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2008-09. Roles of the cation–chloride cotransporters in neurological disease in NATURE REVIEWS NEUROLOGY
  • 1983-07. Sites of action of tripamide in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1999-06. Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter in NATURE GENETICS
  • 2014-09-19. Cation-chloride cotransporters in neuronal development, plasticity and disease in NATURE REVIEWS NEUROSCIENCE
  • 1998-04. The Na-K-Cl Cotransporters in JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
  • 1998-01. Clinical Pharmacokinetics and Pharmacodynamics of Torasemide in CLINICAL PHARMACOKINETICS
  • 1987-02. Na−K−2Cl cotransport in winter flounder intestine and bovine kidney outer medulla: [3H] bumetanide binding and effects of furosemide analogues in THE JOURNAL OF MEMBRANE BIOLOGY
  • 1998-08. The clinical pharmacology of loop diuretics in the pediatric patient in PEDIATRIC NEPHROLOGY
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    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-27995-w

    DOI

    http://dx.doi.org/10.1038/s41598-018-27995-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105107353

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29959396


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