Triflocin, a novel inhibitor for the Na‐HCO₃ symport in the proximal tubule

Abstract

Triflocin, applied at millimolar concentration hyperpolarizes the basolateral membrane of Necturus proximal convoluted tubular cells, in vivo. Barium, 2.5 × 10−3 m, ouabain, 10−3 m, or amiloride 10−4 m, fail to prevent this hyperpolarization. Triflocin has no effect on the intracellular chloride activity. In physiological acid base conditions, Triflocin increases intracellular pH. Upon an acute isohydric hypercapnia, Triflocin depolarizes the basolateral membrane potential. It is concluded that, Triflocin inhibits the basolateral electrogenic Na‐(HCO3)n > 1 cotransport in proximal tubules.

Molecular switch for CLC-K Cl − channel block/activation: Optimal pharmacophoric requirements towards high-affinity ligands

“…The coplanar conformation of the two aromatic rings is the result of the intramolecular hydrogen bond between the amino group and the oxygen atoms of the carboxylic moiety. To induce a distortion of this coplanar arrangement, we synthesized triflocin, a blocker of Na-HCO 3 cotransporters that is used as a diuretic (22), in which the pyridine nitrogen atom is shifted from the ortho to the para position with respect to the amino group, thus allowing a noncoplanar arrangement of the two aromatic moieties due to the steric hindrance resulting from the introduction of an additional hydrogen atom in the ortho position to the aniline nitrogen atom (Fig. 1A).…”

Chloride transport in the renal proximal tubule

“…The lack of a basolateral Cl − pathway allowing Cl − exit from the cell to the interstitium would be a major limitation to transcellular Cl − reabsorption. Putative basolateral G Cl have been approached often by bi-ionic potential measurements, because anionic transport system inhibitors may be poorly specific [19,82]. Upon a sudden reduction in [Cl] pt , membrane depolarization will reflect the presence of G Cl .…”