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: 286/6/G891    most recent 00458.2003v1 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 (6) Citing Articles via Google Scholar Google Scholar Articles by Hirokawa, M. Articles by Kaunitz, J. D. Search for Related Content PubMed PubMed Citation Articles by Hirokawa, M. Articles by Kaunitz, J. D.

MUCOSAL BIOLOGY

Low-dose PGE₂ mimics the duodenal secretory response to luminal acid in mice

¹Greater Los Angeles Veterans Affairs Healthcare System, ²Center for Ulcer Research and Education: Digestive Diseases Research Center, Los Angeles 90073; ³Department of Medicine, School of Medicine, ⁴Department of Biomathematics, University of California, Los Angeles 90024; ⁵Brentwood Biomedical Research Institute, Los Angeles, California 90073

Submitted 24 October 2003 ; accepted in final form 29 January 2004

Luminal exposure to concentrated acid, the most accepted physiological stimulus for duodenal bicarbonate secretion (DBS), cannot be used with in vitro preparations due to potential tissue damage. We thus examined whether exposure to PGE₂, a well-characterized physiological duodenal secretagogue, could mimic the effects of acid perfusion. DBS was measured in C57/BL mice by pH-stat/back-titration and measurement of total dissolved CO₂ concentration ([CO₂]_t). Anion transport inhibitor DIDS, anion channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), carbonic anhydrase inhibitor methazolamide, and nonselective cyclooxygenase inhibitor indomethacin were used to inhibit separate components of HCO₃^– secretory pathway. Baseline DBS was not altered by exposure to methazolamide (0.1 mM) but was slightly reduced by DIDS (0.5 mM). DBS and [CO₂]_t increased after acid and PGE₂ exposure. DIDS (0.5 mM) and NPPB (0.2 mM) abolished acid-induced DBS increase. Methazolamide (0.1 mM) and DIDS inhibited acid-induced [CO₂]_t increase. DIDS, NPPB, or methazolamide had little effect on DBS in response to high concentration PGE₂ (100 µg/ml). Low concentration PGE₂ (1 µg/ml) increased DBS that was inhibited by DIDS, NPPB, and methazolamide. Pretreatment with indomethacin (5 mg/kg) inhibited DBS induced by acid exposure but not by PGE₂. High-dose PGE₂ substantially increases DBS by a mechanism that appears to be different than secretory response to luminal acid perfusion. Secretory response to low-dose PGE₂, at least in terms of inhibitor profile, closely resembles secretion in response to perfusion of physiological acid concentrations and may be a useful stimulus for in vitro study of DBS in isolated mouse duodenum.

luminal acid exposure; in vivo simulation; intestinal ion transport

This article has been cited by other articles:

				Z. M. Sellers, E. Mann, A. Smith, K. H. Ko, R. Giannella, M. B. Cohen, K. E. Barrett, and H. Dong Heat-stable enterotoxin of Escherichia coli (STa) can stimulate duodenal HCO3- secretion via a novel GC-C- and CFTR-independent pathway FASEB J, May 1, 2008; 22(5): 1306 - 1316. [Abstract] [Full Text] [PDF]

				J. G. Kirkland, G. S. Cottrell, N. W. Bunnett, and C. U. Corvera Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G335 - G346. [Abstract] [Full Text] [PDF]

				M. J. Cowan, T. Coll, and J. H. Shelhamer Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE2 dependent through decreases in COX-2 and cPLA2 protein levels J Appl Physiol, October 1, 2006; 101(4): 1127 - 1135. [Abstract] [Full Text] [PDF]