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HORMONES AND SIGNALING

Unique regulation of anion/HCO₃^- exchangers by constitutive nitric oxide in rabbit small intestine

Digestive Diseases Unit, Department of Medicine, The University of Rochester Medical Center, Rochester, New York 14642

Submitted 13 January 2003 ; accepted in final form 14 July 2003

In the rabbit small intestine, there are three functionally different brush-border membrane (BBM) anion/HCO₃^- exchangers: 1) Cl/HCO₃^- exchange on the BBM of villus cells responsible for coupled NaCl absorption; 2) Cl/HCO₃^- exchange on the BBM of crypt cells possibly involved in HCO₃^- secretion; and 3) short-chain fatty acid (SCFA)/HCO₃^- exchange on the BBM of villus cells, which facilitates SCFA absorption. Although constitutive nitric oxide (cNO) has been postulated to alter many gastrointestinal tract functions, how cNO may specifically alter these three transporters is unknown. Inhibition of cNO synthase with N^G-nitro-L-arginine methyl ester (L-NAME) 1) did not affect villus cell BBM Cl/HCO₃ change, 2) stimulated crypt cell BBM Cl/HCO₃^- exchange, and 3) inhibited villus cell BBM SCFA/HCO₃^- exchange. D-NAME, an inactive analog of L-NAME, and L-N⁶-(1-iminoethyl)lysine, a more selective inhibitor of inducible NO, did not affect these transport processes. Kinetic studies demonstrated that 1) the mechanism of inhibition of crypt cell BBM Cl/HCO₃^- exchange is secondary to a decrease in the maximal rate of uptake of Cl, without an alteration in the affinity of the transporter for Cl, and 2) the mechanism of stimulation of villus cell BBM SCFA/HCO₃^- exchange is secondary to an increase in the affinity of the transporter for SCFA without an alteration in the maximal rate of uptake of SCFA. These results indicate that cNO uniquely regulates the three BBM anion/HCO₃^- transporters in the rabbit small intestine.

brush border; intestinal absorption; short-chain fatty acid transport; secretion

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