HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/1/G102    most recent 00092.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Furukawa, O. Articles by Kaunitz, J. D. Search for Related Content PubMed PubMed Citation Articles by Furukawa, O. Articles by Kaunitz, J. D.

MUCOSAL BIOLOGY

NHE3 inhibition activates duodenal bicarbonate secretion in the rat

¹Greater Los Angeles Veterans Affairs Healthcare System, ²Department of Medicine, School of Medicine, and ³Department of Biomathematics, University of California Los Angeles, ⁴San Fernando Valley Internal Residency Program, and ⁵CURE: Digestive Diseases Research Center, Los Angeles, California 90073

Submitted 21 February 2003 ; accepted in final form 18 July 2003

We examined the effect of inhibition of Na⁺/H⁺ exchange (NHE) on duodenal bicarbonate secretion (DBS) in rats to further understand DBS regulation. DBS was measured by using the pH-stat method and by using CO₂-sensitive electrodes. 5-(N,N-dimethyl)-amiloride (50 µM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS. Nevertheless, 3 mM DMA, a higher concentration that inhibits NHE1, NHE2, and NHE3, significantly increased DBS. Moreover, S1611 and S3226, both specific inhibitors of NHE3 only, or perfusion with Na⁺-free solutions, dose dependently increased DBS, as measured by pH-stat and CO₂-sensitive electrode, without affecting intracellular pH. Coperfusion with 0.1 µM indomethacin, 0.5 mM DIDS, or 1 mM methazolamide did not affect S3226-induced DBS. Nevertheless, coperfusion with 0.1 and 0.3 mM 5-nitro-2-(3-phenylpropylamino) benzoic acid, which inhibits the cystic fibrosis transmembrane conductor regulator (CFTR), dose dependently inhibited S3226-induced DBS. In conclusion, only specific apical NHE3 inhibition increased DBS, whereas prostaglandin synthesis, cotransporter activation, or intracellular formation by carbonic anhydrase was not involved. Because NHE3 inhibition-increased DBS was inhibited by an anion channel inhibitor and because reciprocal CFTR regulation has been previously shown between NHE3 and apical membrane anion transporters, we speculate that NHE3 inhibition increased DBS by altering anion transporter function.

epithelial cells; cystic fibrosis transmembrane conductance regulator; back titration; S3226

This article has been cited by other articles:

				M. Mizumori, Y. Choi, P. H. Guth, E. Engel, J. D. Kaunitz, and Y. Akiba CFTR inhibition augments NHE3 activity during luminal high CO2 exposure in rat duodenal mucosa Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1318 - G1327. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				J. E. Simpson, C. W. Schweinfest, G. E. Shull, L. R. Gawenis, N. M. Walker, K. T. Boyle, M. Soleimani, and L. L. Clarke PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of the murine duodenum Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1079 - G1088. [Abstract] [Full Text] [PDF]

				M. Mizumori, J. Meyerowitz, T. Takeuchi, S. Lim, P. Lee, C. T. Supuran, P. H. Guth, E. Engel, J. D. Kaunitz, and Y. Akiba Epithelial carbonic anhydrases facilitate PCO2 and pH regulation in rat duodenal mucosa J. Physiol., June 15, 2006; 573(3): 827 - 842. [Abstract] [Full Text] [PDF]

				O. Furukawa, M. Hirokawa, L. Zhang, T. Takeuchi, L. C. Bi, P. H. Guth, E. Engel, Y. Akiba, and J. D. Kaunitz Mechanism of augmented duodenal HCO3- secretion after elevation of luminal CO2 Am J Physiol Gastrointest Liver Physiol, March 1, 2005; 288(3): G557 - G563. [Abstract] [Full Text] [PDF]

				C. L. Brett, M. Donowitz, and R. Rao Evolutionary origins of eukaryotic sodium/proton exchangers Am J Physiol Cell Physiol, February 1, 2005; 288(2): C223 - C239. [Abstract] [Full Text] [PDF]

				A. Allen and G. Flemstrom Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin Am J Physiol Cell Physiol, January 1, 2005; 288(1): C1 - C19. [Abstract] [Full Text] [PDF]

				M. E. Krouse, J. F. Talbott, M. M. Lee, N. S. Joo, and J. J. Wine Acid and base secretion in the Calu-3 model of human serous cells Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1274 - L1283. [Abstract] [Full Text] [PDF]