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Am J Physiol Gastrointest Liver Physiol 280: G216-G221, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 2, G216-G221, February 2001

Effect of E. coli heat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice

Alan N. Charney1, Richard W. Egnor1, Jesline T. Alexander-Chacko1, Valentin Zaharia1, Elizabeth A. Mann2, and Ralph A. Giannella2

1 Nephrology Section, Veterans Affairs Medical Center and New York University School of Medicine, New York, New York 10010; and 2 Division of Digestive Diseases, Veterans Affairs Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3- Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+ absorption, lower net Cl- absorption, and a negative residual ion flux (JR), indicating net HCO3- absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl- (Jsright-arrow mCl) and decreased net Cl- flux (JnetCl) accompanied by increases in short-circuit current (Isc), potential difference (PD), and tissue conductance (G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon Jsright-arrow mCl and JnetCl, Isc, PD, G, and JR similar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.

sodium and chloride ion fluxes; guanosine 3',5'-cyclic monophosphate; anion secretion


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