A new member of the HCO3(-) transporter superfamily is an apical anion exchanger of beta-intercalated cells in the kidney.
The kidneys play pivotal roles in acid-base homeostasis, and the acid-secreting (alpha-type) and bicarbonate-secreting (beta-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 alpha- and beta-intercalated cells are interchangeable via a cell polarity change. Immunohistological studies, however, have failed to confirm that the apical anion exchanger of beta-intercalated cells is the band 3 protein localized to the basolateral membrane of alpha-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 beta-intercalated cells. Cloned cDNA from the beta-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 beta-intercalated cells, although some beta-intercalated cells were negative for AE4 staining. We conclude that our newly cloned transporter is an apical anion exchanger of the beta-intercalated cells, whereas our data do not exclude the possibility that there may be another form of anion exchanger in these cells.
Tsuganezawa
H
H
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Kobayashi
K
K
Iyori
M
M
Araki
T
T
Koizumi
A
A
Watanabe
S
S
Kaneko
A
A
Fukao
T
T
Monkawa
T
T
Yoshida
T
T
Kim
D K
DK
Kanai
Y
Y
Endou
H
H
Hayashi
M
M
Saruta
T
T
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D001639:Bicarbonates / Q000378:metabolism*; D019556:COS Cells; D002245:Carbon Dioxide / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
D017920:Antiporters; D001639:Bicarbonates; D002712:Chlorides; D012333:RNA, Messenger; D002245:Carbon Dioxide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid