AI Article Synopsis

  • The study identifies three potential contributors to chloride (Cl(-)) entry in parietal cells, including the DIDS-sensitive Cl(-)/HCO(3)(-) exchanger AE2, SLC26A7 protein, and the Na(+)-2Cl(-)K(+) cotransporter (NKCC1).
  • Researchers monitored Cl(-) influx and pH changes in hand-dissected rat gastric glands using various ion content manipulations and pharmacological inhibitors, confirming SLC26A7 expression in parietal cells through imaging techniques.
  • Results show SLC26A7 plays a key role in Cl(-) uptake during histamine stimulation, while the NKCC1 inhibitor

Article Abstract

To date three potential candidates for parietal cell basolateral Cl(-) entry have been described: the highly 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive Cl(-)/HCO(3)(-) exchanger AE2, the HCO(3)(-) and lowly DIDS-sensitive SLC26A7 protein, and the Na(+)-2Cl(-)K(+) cotransporter (NKCC1). In this study we investigate the contribution of these pathways to secretagogue stimulated acid secretion. Individually hand-dissected rat gastric glands were microfluorimetrically monitored for Cl(-) influx and pH(i) changes. Transporter activity was determined by varying ion content and through the use of pharmacological inhibitors. Expression of SLC26A7 in rat parietal cells was shown by immunohistochemistry and Western blot. SLC26A7 was inhibited by 5-Nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB) (100 microM) in the Xenopus laevis oocyte expression system. Cl(-) influx in parietal cells was enhanced by histamine, depended partially on endogenous HCO(3)(-) synthesis and completely on extracellular Na(+). Removal and subsequent readdition of Cl(-) revealed a low and a high DIDS-sensitive HCO(3)(-) extrusion system contributing to Cl(-) uptake. At acidic pH(i), however, H(+) extrusion via the H(+),K(+)-ATPase depending on Cl(-) uptake was abolished only in the presence of 100 microM (NPPB) and at high (250 microM) DIDS concentration. There was no effect of the NKCC inhibitor bumetanide on stimulated H(+) extrusion. These results would be compatible with SLC26A7 as a Cl(-) uptake system under histamine stimulation.

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http://dx.doi.org/10.1007/s00424-007-0254-yDOI Listing

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