Cl channel blockers inhibit the volume-activated efflux of Cl and taurine in cultured neurons

Abstract

The effects of the Cl channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 1,9-dideoxyforskolin (DDF), dipyridamole, and niflumic acid and of the polyunsaturated fatty acids arachidonic, linolenic, and linoleic acids on regulatory volume decrease (RVD) and associated 125I and [3H]taurine fluxes in cultured rat cerebellar granule neurons were examined. Dose-response curves of NPPB, DDF, and dipyridamole showed 20-100% inhibition of RVD and osmolyte fluxes. Niflumic acid was less potent, requiring 150-600 microM to show effects of this magnitude. The polyunsaturated fatty acids (5-20 microM) inhibited 80-90% RVD and osmolyte fluxes, with arachidonic acid exhibiting the most potent effect. The volume-associated taurine efflux was somewhat higher in younger neurons, but the pharmacological sensitivity was essentially the same in immature and mature cells. The effects of all tested drugs on 125I and [3H]taurine fluxes were remarkably similar, indicating a close pharmacological sensitivity of the transport mechanism for the two osmolytes. This is in line with the suggestion of a common pathway for the volume-associated release of Cl and amino acids functioning as osmolytes.

Volume changes and whole cell membrane currents activated during gradual osmolarity decrease in C6 glioma cells: contribution of two types of K+ channels

“…This is in marked contrast with the early activation of a Cl Ϫ current. This result strongly supports the notion of different permeability pathways for the two osmolytes (4,20) and provides further evidence against a common pathway for amino acids and Cl Ϫ efflux, which was based mainly on similarities in their pharmacological profile (17,19). The sensitivity to Cl Ϫ channel blockers, however, is suggestive of some interdependence of the two osmolyte pathways.…”

Stimulation by caveolin-1 of the hypotonicity-induced release of taurine and ATP at basolateral, but not apical, membrane of Caco-2 cells

“…4A, the basolateral taurine efflux during hypotonicity was markedly higher in k14 than in WT Caco-2 cells, reaching a peak value of 17.1 Ϯ 2.0 min Ϫ1 (achieved after 20 min of HTS) vs. 11.7 Ϯ 1.3 min Ϫ1 (achieved after 24 min of HTS), respectively (n ϭ 6; P Ͻ 0.05). Application of 100 M NPPB, a well-characterized blocker of I Cl,swell and taurine efflux (13,32) inhibited the basolateral hypotonicityinduced taurine efflux both in WT and in k14 Caco-2 cells (Fig. 4A).…”

Receptor Regulation of the Volume-Sensitive Efflux of Taurine and Iodide from Human SH-SY5Y Neuroblastoma Cells: Differential Requirements for Ca2+ and Protein Kinase C

“…The possibility that the volume-sensitive release of Cl Ϫ and organic osmolytes occurs via a common membrane channel (VSOAC) has received support primarily on the basis of the similarities of pharmacological inhibition profiles obtained in the presence of a variety of nonselective anion channel blockers (Banderali and Roy, 1992;Jackson and Strange, 1993;Sanchez-Olea et al, 1996;Abdullaev et al, 2006). However, in some tissues, the existence of separate Cl Ϫ and taurine efflux pathways has also been proposed (Lambert and Hoffman, 1994;Stutzin et al, 1999;Shennan and Thomson, 2000;Tomassen et al, 2004).…”