Different acid secretagogues activate different Na+/H+ exchanger isoforms in rabbit parietal cells
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 agonis...
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Published in: | The American journal of physiology Vol. 275; no. 5; pp. G1085 - G1093 |
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Main Authors: | , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
01-11-1998
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Online Access: | Get full text |
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Summary: | 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 microM 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 microM) reduced forskolin-stimulated Na+/H+ exchange activity by 35%, and 25 microM HOE-642 (inhibits NHE1 and -2) inhibited an additional 13%, but 500 microM 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0002-9513 |
DOI: | 10.1152/ajpgi.1998.275.5.G1085 |