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J. Biol. Chem., Vol. 276, Issue 11, 8180-8189, March 16, 2001
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From the The kidneys play pivotal roles in acid-base
homeostasis, and the acid-secreting ( The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AB038263 and AB038264.
A New Member of the HCO
-Intercalated Cells in the Kidney*
,,,,,,,**, and
Department of Internal Medicine and the
§ Department of Physiology, Keio University School of
Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 and the
¶ Department of Pharmacology and Toxicology, Kyorin University
School of Medicine, 6-20-2 Shinnkawa, Mitaka City,
Tokyo 181-8611, Japan
-type) and
bicarbonate-secreting (
-type) intercalated cells in the collecting
ducts are major sites for the final modulation of urinary acid
secretion. Since the H+-ATPase and anion exchanger
activities in these two types of intercalated cells exhibit opposite
polarities, it has been suggested that the - and -intercalated
cells are interchangeable via a cell polarity change.
Immunohistological studies, however, have failed to confirm that the
apical anion exchanger of -intercalated cells is the band 3 protein
localized to the basolateral membrane of -intercalated cells. In the
present study, we show the evidence that a novel member of the anion
exchanger and sodium bicarbonate cotransporter superfamily is an apical
anion exchanger of -intercalated cells. Cloned cDNA from the
-intercalated cells shows about 30% homology with anion exchanger
types 1-3, and functional expression of this protein in COS-7 cells
and Xenopus oocytes showed sodium-independent and
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-insensitive anion
exchanger activity. Furthermore, immunohistological studies revealed
that this novel anion exchanger is present on the apical membrane of
-intercalated cells, although some -intercalated cells were
negative for AE4 staining. We conclude that our newly cloned
transporter is an apical anion exchanger of the -intercalated cells,
whereas our data do not exclude the possibility that there may be
another form of anion exchanger in these cells.
*
This work was supported in part by grants from the Ministry
of Education, Science, and Culture of Japan, and a National
grant-in-aid for the Establishment of High-Tech Research Center in a
Private University.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.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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