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J. Biol. Chem., Vol. 276, Issue 29, 27042-27050, July 20, 2001
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From the Multiple Na+/H+
exchangers (NHEs) are expressed in salivary gland cells; however, their
functions in the secretion of saliva by acinar cells and the subsequent
modification of the ionic composition of this fluid by the ducts are
unclear. Mice with targeted disruptions of the Nhe1,
Nhe2, and Nhe3 genes were used to study
the in vivo functions of these exchangers in parotid
glands. Immunohistochemistry indicated that NHE1 was localized
to the basolateral and NHE2 to apical membranes of both acinar and duct
cells, whereas NHE3 was restricted to the apical region of duct cells.
Na+/H+ exchange was reduced more than 95% in
acinar cells and greater than 80% in duct cells of NHE1-deficient mice
(Nhe1
Defective Fluid Secretion and NaCl Absorption in the Parotid
Glands of Na+/H+ Exchanger-deficient Mice*
§¶,§¶
,§¶,,,, and§¶¶
Center for Oral Biology, Rochester Institute
of Biomedical Sciences, and the § Eastman Department of
Dentistry, University of Rochester Medical Center, Rochester, New York
14642, the §§ Department of Pediatric Dentistry,
University of Connecticut, Farmington, Connecticut 06030, the
Department of Molecular Genetics,
Biochemistry and Microbiology, University of Cincinnati College of
Medicine, Cincinnati, Ohio 45267, and the ** Division of Developmental
Biology, Children's Hospital Research Foundation, Cincinnati, Ohio
45229
/). Salivation in response to
pilocarpine stimulation was reduced significantly in both
Nhe1/ and Nhe2/
mice, particularly during prolonged stimulation, whereas the loss of
NHE3 had no effect on secretion. Expression of
Na+/K+/2Cl cotransporter mRNA
increased dramatically in Nhe1/ parotid
glands but not in those of Nhe2/ or
Nhe3/ mice, suggesting that compensation
occurs for the loss of NHE1. The sodium content, chloride activity and
osmolality of saliva in Nhe2/ or
Nhe3/ mice were comparable with those of
wild-type mice. In contrast, Nhe1/ mice
displayed impaired NaCl absorption. These results suggest that in
parotid duct cells apical NHE2 and NHE3 do not play a major role in
Na+ absorption. These results also demonstrate that
basolateral NHE1 and apical NHE2 modulate saliva secretion in
vivo, especially during sustained stimulation when secretion
depends less on Na+/K+/2Cl
cotransporter activity.
*
This work was supported in part by National Institutes of
Health Grants DK50594 (to G. E. S.), DE08921, and DE09692 (to
J. E. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Unilever Research, Port Sunlight Laboratory,
Quarry Rd. East, Bebington, Wirral CH63 3JW, United Kingdom. E-mail:
Richard.Evans@Unilever.com.
¶¶
To whom correspondence should be addressed: Center for
Oral Biology, Univ. of Rochester, Medical Center Box 611, 601 Elmwood Ave., Rochester, NY 14642. Tel.: 716-275-3444; Fax: 716-473-2679; E-mail: james_melvin@urmc.rochester.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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