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Am J Physiol Gastrointest Liver Physiol 275: G1085-G1093, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 5, G1085-G1093, November 1998

Different acid secretagogues activate different Na+/H+ exchanger isoforms in rabbit parietal cells

O. Bachmann1, T. Sonnentag1, W.-K. Siegel1, G. Lamprecht1, A. Weichert2, M. Gregor1, and U. Seidler1

1 Department of Internal Medicine I, University Hospital Schnarrenberg, Eberhard-Karls University Tübingen, D-72076 Tübingen; and 2 Hoechst AG, D-65926 Frankfurt, Germany

Rabbit parietal cells express three Na+/H+ exchanger isoforms (NHE1, NHE2, and NHE4). We investigated the effects of carbachol, histamine, and forskolin on Na+/H+ exchange activity and acid formation in cultured rabbit parietal cells and tested the effect of NHE isoform-specific inhibition on agonist-induced Na+/H+ exchange. Carbachol (10-4 M) was the weakest acid secretagogue but caused the strongest Na+/H+ exchange activation, which was completely blocked by 1 µM HOE-642 (selective for NHE1); histamine (10-4 M) and forskolin (10-5 M) were stronger stimulants of [14C]aminopyrine accumulation but weaker stimulants of Na+/H+ exchange activity. HOE-642 (1 µM) reduced forskolin-stimulated Na+/H+ exchange activity by 35%, and 25 µM HOE-642 (inhibits NHE1 and -2) inhibited an additional 13%, but 500 µM dimethyl amiloride (inhibits NHE1, -2, and -4) caused complete inhibition. The presence of 5% CO2-HCO-3 markedly reduced agonist-stimulated H+ efflux rates, suggesting that the anion exchanger is also activated. Hyperosmolarity also activated Na+/H+ exchange. Our data suggest that, in rabbit parietal cells, Ca2+-dependent stimulation causes a selective activation of NHE1, whereas cAMP-dependent stimulation activates NHE1, NHE2, and more strongly NHE4. Because intracellular pH (pHi) did not change in the presence of CO2-HCO-3 and concomitant activation of Na+/H+ and anion exchange is one of the volume regulatory mechanisms, we speculate that the physiological significance of secretagogue-induced Na+/H+ exchange activation may not be related to pHi but to volume regulation during acid secretion.

NHE1; NHE2; NHE4; stomach; acid secretion; histamine; forskolin; carbachol; intracellular pH; volume regulation


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