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1 Dalton Cardiovascular Research Center and Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri 65211; and 2 Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Sodium/proton exchangers
[Na+/H+ (NHEs)] play an important role
in salt and water absorption from the intestinal tract. To investigate the contribution of the apical membrane NHEs, NHE2 and NHE3, to electroneutral NaCl absorption, we measured radioisotopic
Na+ and Cl
flux across isolated jejuna from
wild-type [NHE(+)], NHE2 knockout [NHE2(
)], and NHE3 knockout
[NHE3()] mice. Under basal conditions, NHE(+) and NHE2() jejuna
had similar rates of net Na+ (~6
µeq/cm2 · h) and Cl (~3
µeq/cm2 · h) absorption. In contrast, NHE3()
jejuna had reduced net Na+ absorption (~2
µeq/cm2 · h) but absorbed Cl at
rates similar to NHE(+) and NHE2() jejuna. Treatment with 100 µM
5-(N-ethyl-N-isopropyl) amiloride (EIPA)
completely inhibited net Na+ and Cl
absorption in all genotypes. Studies of the Na+ absorptive
flux (J
) jejunum was
equally sensitive to 1 and 100 µM EIPA. Treatment with forskolin/IBMX
to increase intracellular cAMP (cAMPi) abolished net NaCl
absorption and stimulated electrogenic Cl secretion in
all three genotypes. Quantitative RT-PCR of epithelia from NHE2() and
NHE3() jejuna did not reveal differences in mRNA expression of NHE3
and NHE2, respectively, when compared with jejunal epithelia from
NHE(+) siblings. We conclude that 1) NHE3 is the dominant
NHE involved in small intestinal Na+ absorption;
2) an amiloride-sensitive Na+ transporter
partially compensates for Na+ absorption in NHE3()
jejunum; 3) cAMPi stimulation abolishes net
Na+ absorption in NHE(+), NHE2(), and NHE3() jejunum;
and 4) electroneutral Cl absorption is not
directly dependent on either NHE2 or NHE3.
sodium; chloride; cystic fibrosis transmembrane conductance regulator; adenosine 3',5'-cyclic monophosphate; chloride-bicarbonate exchanger; sodium-hydrogen exchange; jejunum; small intestine; cystic fibrosis
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