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: 288/5/G956    most recent 00441.2004v1 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 Hoque, K. M. Articles by Binder, H. J. Search for Related Content PubMed PubMed Citation Articles by Hoque, K. M. Articles by Binder, H. J.

MUCOSAL BIOLOGY

Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum

Department of Internal Medicine, Yale University, New Haven, Connecticut

Submitted 29 September 2004 ; accepted in final form 14 December 2004

Zn, an essential micronutrient and second most abundant trace element in cell and tissues, reduces stool output when administered to children with acute diarrhea. The mechanism by which Zn improves diarrhea is not known but could result from stimulating Na absorption and/or inhibiting anion secretion. The aim of this study was to investigate the direct effect of Zn on intestinal epithelial ion absorption and secretion. Rat ileum was partially stripped of serosal and muscle layers, and the mucosa was mounted in lucite chambers. Potential difference and short-circuit current were measured by conventional current-voltage clamp method. ⁸⁶Rb efflux and uptake were assessed for serosal K channel and Na-K-2Cl cotransport activity, respectively. Efflux experiments were performed in isolated cells preloaded with ⁸⁶Rb in the presence of ouabain and bumetanide, whereas uptake experiments were performed in low-Cl isotonic buffer containing Ba and ouabain. Neither mucosal nor serosal Zn affected glucose-stimulated Na absorption. In contrast, forskolin-induced Cl secretion was markedly reduced by serosal but not mucosal addition of Zn. Zn also substantially reversed the increase in Cl secretion induced by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) with half-maximal inhibitory concentration of 0.43 mM. In contrast, serosal Zn did not alter Cl secretion stimulated by carbachol, a Ca-dependent agonist. Zn inhibited 8-BrcAMP-stimulated ⁸⁶Rb efflux but not carbachol-stimulated ⁸⁶Rb efflux. Zn had no effect on bumetanide-sensitive ⁸⁶Rb uptake, Na-K-ATPase, or CFTR. We conclude from these studies that Zn inhibits cAMP-induced Cl secretion by blocking basolateral membrane K channels.

enterocyte; ⁸⁶Rb efflux; ⁸⁶Rb uptake; K-channel inhibitors

This article has been cited by other articles:

				M. Lazzerini Zinc supplements for severe cholera BMJ, February 2, 2008; 336(7638): 227 - 228. [Full Text] [PDF]

				M. Lukacik, R. L. Thomas, and J. V. Aranda A Meta-analysis of the Effects of Oral Zinc in the Treatment of Acute and Persistent Diarrhea Pediatrics, February 1, 2008; 121(2): 326 - 336. [Abstract] [Full Text] [PDF]

				J. K. Crane, T. M. Naeher, I. Shulgina, C. Zhu, and E. C. Boedeker Effect of Zinc in Enteropathogenic Escherichia coli Infection Infect. Immun., December 1, 2007; 75(12): 5974 - 5984. [Abstract] [Full Text] [PDF]

				P. J. Bajwa, A. Alioua, J. W. Lee, D. S. Straus, L. Toro, and C. Lytle Fenofibrate inhibits intestinal Cl secretion by blocking basolateral KCNQ1 K+ channels Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1288 - G1299. [Abstract] [Full Text] [PDF]

				J. K. Crane, S. S. Choudhari, T. M. Naeher, and M. E. Duffey Mutual Enhancement of Virulence by Enterotoxigenic and Enteropathogenic Escherichia coli Infect. Immun., March 1, 2006; 74(3): 1505 - 1515. [Abstract] [Full Text] [PDF]