Inhibition of the Na/bicarbonate cotransporter NBCe1-A by diBAC oxonol dyes relative to niflumic acid and a stilbene

Academic Article

Abstract

  • Na/HCO cotransporters (NBCs) are important regulators of intracellular pH (pH ) in a variety of organ systems where acid-base status is critical for tissue function. To characterize the pharmacology of NBCs in more detail, we used the two-electrode voltage-clamp technique to examine the effect of previously identified inhibitors of anion exchanger 1 (AE1) on the activity of rat NBCe1-A expressed in Xenopus laevis oocytes. NBC-expressing oocytes voltage-clamped at -60 mV and exposed to a 5% CO /33 mM HCO solution displayed NBC-mediated outward currents that were inhibited by either niflumic acid or one of the two bis-oxonol dyes diBA(3)C4 and diBA(5)C4. NBCe1-A was less sensitive to niflumic acid (apparent K of 100 μM) than 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS, apparent K of 36 μM) but more sensitive to the diBAC dyes (apparent K of ∼10 μM). Based on current-voltage relationships, the diBAC dyes inhibited HCO -induced NBCe1-mediated inward currents more so than outward currents. NBCe1 sensitivity to the dyes was (1) lower in the presence of 40 μM DIDS, (2) unaffected by changes in external HCO concentration and (3) only modestly higher at an external Na concentration of 5, but not 15 or 33, mM. Therefore, the diBAC dyes compete with DIDS but not appreciably with Na or HCO for binding. The mechanism of diBAC inhibition of NBCe1 appears similar to that previously reported for AE1. © 2007 Springer Science+Business Media, LLC. 3 i 2 3 i i i 3 3 3 - - - + + -
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    Digital Object Identifier (doi)

    Author List

  • Liu X; Williams JB; Sumpter BR; Bevensee MO
  • Start Page

  • 195
  • End Page

  • 204
  • Volume

  • 215
  • Issue

  • 2-3