| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
3
cotransporter
Departments of 1 Medicine and
2 Molecular Genetics, We recently reported the cloning and expression of a human
kidney
Na+-HCO
proximal tubule; bicarbonate; acidosis; alkalosis
PROXIMAL TUBULE acidification processes are responsible
for the reabsorption of most of the
HCO Although the previously reported human NBC-1 cDNA clone (6) may be
useful in studying
Na+-HCO Isolation and Characterization of the Rat NBC-1 cDNA
ABSTRACT
Top
Abstract
Introduction
Procedures
Results
Discussion
References
3
cotransporter (NBC-1) (C. E. Burnham, H. Amlal, Z. Wang,
G. E. Shull, and M. Soleimani. J. Biol.
Chem. 272: 19111-19114, 1997). To expedite in vivo
experimentation, we now report the cDNA sequence of rat kidney NBC-1.
In addition, we describe both the organ and nephron segment
distributions and the regulation of NBC-1 mRNA under three models of pH
stress: chloride-depletion alkalosis (CDA), metabolic acidosis, and
bicarbonate loading. Rat NBC-1 cDNA encodes an open reading frame of
1,035 amino acids, with 96 and 87% identity to human and salamander NBC-1, respectively. Rat NBC-1 mRNA is expressed at high levels in
kidney and brain, with lower levels in colon, stomach, and heart. None
appears in liver. In the kidney, NBC-1 is expressed mainly in the
proximal tubule, with traces found in medullary thick ascending limb
and papilla. HCO3 loading decreased
NBC-1 mRNA levels, which were unchanged either by metabolic acidosis or
by CDA.
INTRODUCTION
Top
Abstract
Introduction
Procedures
Results
Discussion
References
3 present in the glomerular
filtrate (13, 18, 26). The bulk of this reabsorption occurs via
transcellular coupling of the luminal Na+/H+
exchanger (NHE-3) with the basolateral
Na+-HCO3
cotransporter (NBC-1). The proximal tubule basolateral membrane NBC is
an electrogenic transporter with an apparent stoichiometry of three
HCO3 per
Na+ ion (25, 28). Recent studies
have suggested that its actual ionic mechanism may involve the
cotransport of Na+,
CO3, and
HCO3 in a 1:1:1 ratio on distinct
sites, consistent with a stoichiometry of three equivalents of base per
Na+ (22). In addition to the
reabsorption of HCO3 in the proximal
tubule,
Na+-HCO3
cotransport plays an important role in cell pH regulation in other
tissues, including heart, brain, liver, and stomach (4, 5, 19, 23).
3
cotransport at the cellular level, using human cell lines, studies in
the whole animal would be expedited by the availability of the rat cDNA
sequence. Accordingly, a human expressed sequence tag (EST) homologous
to the anion exchanger (AE) family (14) was used to screen a rat kidney
cDNA library. A single clone (rNBC-1), with an insert of 3,484 nucleotides, was identified, which was clearly the rat homolog of human
NBC-1. The cDNA clone was then used as a probe in Northern
hybridization experiments to study mRNA distribution and regulation of
mRNA levels in three different in vivo models of pH stress. In the kidney, most rNBC-1 is expressed in the proximal tubule and shows adaptive regulation in HCO3 loading,
but it is not affected by 24 or 48 h of chloride-depletion alkalosis (CDA) or 4 days of metabolic acidosis.
EXPERIMENTAL PROCEDURES
Top
Abstract
Introduction
Procedures
Results
Discussion
References
3
cotransporter cDNA. The probe was generated by PCR amplification of the
same human
Na+-HCO3
cotransporter EST (GenBank accession no. W-39298) that was used to
clone the full-length human NBC-1 cDNA (6). The procedures used for
screening the library and purifying the rNBC-1 cDNA were essentially
identical to those described previously for cloning of AE isoforms
(14). Automated DNA sequence analysis was performed, using Perkin-Elmer
ABI Prism dye-termination technology.
Animal Models
Metabolic acidosis. Rats were placed on NH4Cl (280 mM, added to their drinking water) for 4 days. Both normal and acidotic groups were fed normal Purina rat chow and were killed on the same day. Plasma samples for HCO3 determination by calorimetric
assay were taken at the time of death.
Chloride-depletion alkalosis. Chloride
was selectively depleted by 30 min of peritoneal dialysis against 150 mM NaHCO3. This results in a
severe and sustained alkalosis, as established by previous studies (9).
After dialysis, the rats were allowed free access to distilled
H2O and a low-Cl diet (ICN,
Cleveland, OH). They were killed after 24 or 48 h. Generation of CDA
was confirmed by a significant elevation in plasma
HCO3 concentration
([HCO3]) and a concomitant
reduction in plasma Cl
concentration
([Cl]) (see
RESULTS). Controls were anesthetized
and dialyzed vs. 150 mM NaCl. CDA was confirmed by showing complete
correction of alkalosis with NaCl, as described previously (27).
HCO3
loading.
NaHCO3 (280 mM) was added to the
rats' drinking water, and the rats were given free access to it for 5 days (11, 16). The control group was given normal drinking water. After
5 days, the rats were killed, serum bicarbonate concentration was
measured, and the kidneys were removed for mRNA preparation.
Tubule Suspensions
Proximal tubule. Kidney cortices were removed and proximal tubule suspensions were isolated as described (24).Medullary thick ascending limb. Kidney medullary thick ascending limb (MTAL) tubule suspensions were isolated as previously described (3). In brief, kidneys were sliced open lengthwise and placed in ice-cold Hanks' solution containing (in mM) 137 NaCl, 5.4 KCl, 25 NaHCO3, 0.3 Na2HPO4, 0.4 KH2PO4, 0.5 MgCl2, 10 HEPES, 5 glucose, 5 leucine, and 1 mg/ml bovine serum albumin, which was then bubbled with 95% O2-5% CO2 until pH 7.38 was obtained. Small slices from the inner stripe of the outer medulla were then incubated at 37°C in Hanks' solution containing collagenase. The MTAL tubules were then harvested by sieving the supernatant through a nylon mesh. The final suspension contained almost exclusively MTAL tubules of 75-200 µm of length (>95%) with occasional thin descending limb fragments and negligible amounts of medullary collecting tubules.
Inner medullary collecting duct. Kidney inner medulla (papilla) was isolated and minced, and inner medullary collecting duct (IMCD) suspensions were isolated as described (12).
RNA Isolation and Northern Analysis
RNA was extracted from rat kidney tissue, using TriReagent (Molecular Research, Cincinnati, OH), according to the manufacturer's instructions. The extracted RNA was dissolved in Formazol (Molecular Research), quantitated spectrophotometrically, and stored at
80°C. Total RNA (30 µg/lane) was fractionated on 1.2%
agarose-formaldehyde gels and transferred to nylon membranes. RNA was
covalently bound to the nylon membranes by ultraviolet cross-linking
(7). Hybridization was performed according to the method of Church and
Gilbert (7), using [
-32P]dCTP (NEN, Boston,
MA)-labeled cDNA probes. Radiolabeled blots were exposed overnight to
PhosphorImager storage screens and imaged using ImageQuant software
(Molecular Dynamics).
For purposes of quantitation, blots were probed first with the rNBC-1
probe and then with a human 28S ribosomal RNA (rRNA) cDNA probe. The
latter probe was used as as a measure of gel loading, with the purpose
of being independent of metabolic influences that might affect
glyceraldehyde-3-phosphate dehydrogenase or 
-actin mRNA. Analysis of
hybridization intensities was performed with ImageQuant software, using
grid volume measurement and background subtraction by grid-perimeter
pixel averaging. Image volumes were normalized by dividing each grid
cell volume (NBC-1 or 28S band intensity) by the mean grid cell volume
(band intensity) from the individual blot. Normalized grid cell volumes
for rNBC-1 mRNA were then divided by the normalized 28S rRNA grid cell
volume for the same gel lane (i.e., the same sample) to give the NBC-1 mRNA-to-28S rRNA ratio for that sample. Note that these methods allow a
comparison of NBC-1 mRNA band intensities on an individual Northern
blot but do not allow a comparison of bands on different blots, nor do
they compare the actual molar or microgram amounts of NBC-1 mRNA with
amounts of 28S rRNA.
Statistical Analysis
The data are expressed as means ± SE where appropriate. Statistical significance was measured by the two-sample t-test. Minimal statistical significance was considered to be P < 0.05. Differences with greater P values were deemed not significant (NS).| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Procedures
Results
Discussion
References
|
|---|
Cloning and Characterization of a Rat
Na+-HCO3
Cotransporter cDNA
The complete nucleotide and deduced amino acid sequences are shown in
Fig. 1. The cDNA contains 55 nucleotides of
5'-untranslated sequence, a 3,105-nucleotide open reading frame
encoding a 1,035 amino acid protein, and 320 nucleotides of
3'-untranslated sequence. Because Northern blot analyses
(discussed below) show that the corresponding mRNA is ~8 kb, it is
clear that the cDNA insert lacks much of the untranslated sequence. A
multiple sequence alignment of the deduced amino acid sequence of the
rat kidney cDNA with those of hNBC-1 (6), Ambystoma tigrinum
NBC (aNBC) (20), and the electroneutral
Cl/HCO3
exchanger AE-1 (17) is shown in Fig. 2.
This alignment illustrates the 96% identity between the
deduced amino acid sequence of the rat kidney cDNA and that of the
human kidney
Na+-HCO3
cotransporter cDNA identified previously (6). Note that the rat and
human amino acid sequences can be aligned without gaps and that both
are of the same length (1,035 amino acids). Thus the rat protein is the
homologue of hNBC-1. In addition, the alignment with AE-1 demonstrates
that substantial homology exists between the NBCs and previously
identified members of the AE family.
|
|
Northern Analyses
Gel loading. Figure 3 shows ethidium bromide staining of the RNA loaded into each lane of the gels from which the blots were made that are shown in Figs. 4 and 5, respectively. Each lane is loaded with 30 µg total RNA. Figure 3 demonstrates that each lane had a significant amount of RNA applied to the gel. Therefore, the absence or presence of an rNBC-1 hybridization signal in a given lane is not a result of the absence or presence of RNA in that lane. Note that, in Figs. 6-8, gel loading was quantitated by probing with a human 28S ribosomal RNA (rRNA) cDNA probe as described in EXPERIMENTAL PROCEDURES.
|
|
|
|
|
|
Tissue distribution. Functional
studies have demonstrated the presence of
Na+-HCO3
cotransport in several different tissues. To determine the tissue
distribution of rat NBC-1 mRNA, RNA from heart, brain, stomach, liver,
colon, and kidney was isolated, resolved on a Northern blot, and then
probed with the 2,392-base pair BamH I fragment from
rNBC-1 cDNA (bases 433-2825). As indicated in Fig. 4,
rNBC-1 is highly expressed in kidney and brain. Trace amounts appear in
colon, stomach, and heart, but none appears in liver.
Nephron segment distribution. In
addition to its well-known occurrence in the basolateral membranes of
the proximal tubule, the
Na+-HCO3
cotransporter might mediate the exit of HCO3 across the basolateral membranes
of other nephron segments. We therefore examined the expression of
rNBC-1 in several different nephron segments. RNA was isolated from rat renal cortex, medulla, and from suspensions of proximal tubule, MTAL,
and IMCD. Northern blot analysis (Fig. 5) revealed much greater
expression of rNBC-1 in the cortex than in the medulla, which is
consistent with the observation of a high level of
Na+-HCO3
cotransport in the proximal tubule and much lower levels in MTAL and
IMCD (4, 5).
Metabolic acidosis. Functional studies
in proximal tubule basolateral membrane vesicles prepared from
pretreated rabbits have shown increased rates of
Na+-HCO3
cotransport in acidosis and decreases in alkalosis (1). To examine the
effect of metabolic acidosis on expression of rNBC-1, rats were made
acidotic by the addition of 280 mM
NH4Cl to their drinking water for
5 days. Generation of metabolic acidosis was confirmed by a reduction
in serum [HCO3] from 22.8 ± 1.2 mM in control rats to 14.1 ± 1 mM in acidotic rats
(P < 0.03, n = 3). RNA from the renal
cortices of acidotic animals was isolated and analyzed by Northern
hybridization. As shown in Fig. 6, NBC-1 expression in the kidney was
not significantly different in acidotic rats compared with controls.
Chloride-depletion alkalosis. Rats
were peritoneally dialyzed and killed after 24 (Fig.
7A) and 48 (Fig.
7B) h, as described in
EXPERIMENTAL PROCEDURES. Plasma
[HCO3] increased
(P < 0.05, n = 3) from 22.4 ± 1.5 to 33.4 ± 2 mM, and plasma
[Cl] decreased
(P < 0.05, n = 3) from 96 ± 2.6 to
83 ± 3 mM at 24 h. At 48 h, plasma
[HCO3] increased
(P < 0.05, n = 4) from 23.6 ± 0.7 mM
(control) to 28.1 ± 1.1 mM, and plasma [Cl] decreased
(P < 0.05, n = 4) from 98.2 ± 1.2 to 92.3 ± 1.0 mM. RNA from kidneys of alkalotic rats was isolated and
analyzed by Northern hybridization. As shown in Fig. 7, there was no
significant difference in NBC-1 expression in kidneys of rats after 24 or 48 h of CDA.
HCO3
loading. Rats were given drinking water
containing 280 mM NaHCO3 for 5 days. Plasma [HCO3] was
minimally increased compared with controls, with concentrations of 27.4 ± 1.7 and 23.1 ± 1.5 mM (NS) in experimental and control rats,
respectively. RNA from treated and control rat kidneys was isolated and
analyzed by Northern hybridization. As shown in Fig. 8, NBC-1
expression decreased by 35% (P < 0.05) in kidneys of rats subjected to
HCO3 loading.
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Procedures
Results
Discussion
References
|
|---|
A rat kidney cDNA clone containing the entire open reading frame of the
Na+-HCO3
cotransporter was identified using a human EST to probe a rat kidney
cDNA library. The cDNA clone, containing the entire coding region of a
1,035-amino acid protein, was sequenced and then used as a molecular
probe to determine nephron segment and tissue distribution of rNBC-1 by
Northern analysis. The cloned cDNA contains an open reading frame
encoding 1,035 amino acids, with an estimated molecular mass of 116 kDa
(Fig. 1). The rat and human amino acid sequences showed 96% identity
and could be aligned without gaps (Fig. 2). Tissue distribution studies
showed that, in the rat, NBC-1 is expressed in kidney, heart, stomach, colon, and brain but not liver (Fig. 4). Nephron segment distribution studies showed high expression levels in proximal tubule, with lower
levels in MTAL and IMCD (Fig. 5). Adaptive studies showed downregulation of NBC-1 mRNA in HCO3
loading (Fig. 8). NBC-1 mRNA was very little changed, if at all, either in metabolic acidosis or in CDA (Figs. 6 and 7).
A multiple sequence alignment of the rNBC-1 with hNBC-1, aNBC-1, and human AE-1 demonstrates several important points. The fact that the human and rat sequences align with 96% identity, without insertions or gaps, is a clear indication that the two sequences encode the same protein. The minor differences that do occur may be attributed to species differences alone. In the salamander sequence, despite an 86.5% identity with the rat sequence, the amino terminus diverges sharply from both mammalian sequences. The sequences (although the same length) cannot be aligned without gaps. It might therefore be anticipated that minor functional differences between amphibian and mammalian NBCs would occur in characteristics such as in the relative affinities for substrates (e.g., Na+ vs. Li+) in tissue or membrane targeting, or in response to regulatory mechanisms.
Finally, the substantial homology between the NBCs and the AEs is worth emphasizing. Although the levels of identity between the AE and NBC-1 nucleotide sequences are too low to be used in cloning methodologies that rely on hybridization techniques, the availability of the EST database allows for analysis, and selection of clones at a lower level of similarity. With the use of this technique, it is likely that additional members of this superfamily will be found.
Tissue distribution studies show a somewhat different pattern between
r- and hNBC-1s (6). Both have a high level of expression in kidney, but
rat brain has a much higher level of expression (relative to kidney)
than human. Because both Clontech (the source of the human brain RNA
used in the previous study; Ref. 6) and we used whole brain as a source
of RNA, we conclude that there may be significant differences in
HCO3 transport mechanisms between rat
and human brain. However, the enormous difference in brain mass between
the two species leaves open the possibility that the relatively greater
proportion of a surface structure in the rat, such as the
dura mater, may account for the differences in relative levels of
expression.
Colon, stomach, and heart show weak hybridization signals. There is no apparent expression in rat liver, but it remains possible that significant levels of expression may occur in rat liver under abnormal conditions. The fact that the NBC-1 mRNA is the same size in each tissue suggests that these are not different isoforms, since the large 3' noncoding region might be expected to be altered in the evolution of different isoforms.
A major difference with respect to the functional mode of
Na+-HCO3
cotransport in kidney and other tissues is its direction of transport.
In kidney, NBC-1 mediates the exit of
HCO3 from the cell to the blood (4, 5, 19, 23), whereas, in nonepithelial cells, such as heart (15), and
nonrenal epithelial cells, such as liver (8), as yet unidentified HCO3 transporters mediate the entry of
HCO3 from the blood into the cell.
Whether the difference in the direction of NBC-mediated
HCO3 movement between kidney and other
tissues is caused by differences in cell characteristics, such as
membrane potential or ionic composition, or is due to the presence of
different isoforms of HCO3
transporter, remains to be determined.
NBC-1 is responsible for most of the
HCO3 transport across the basolateral
membrane of the kidney proximal tubule. Nephron segment mRNA
distribution studies revealed that NBC-1 is highly expressed in
proximal tubule, with lower but detectable levels in MTAL. Functional
evidence for the presence of NBC-1 or other
Na+-HCO3
cotransporter isoforms in segments other than proximal tubule is
lacking in the rat. Although the MTAL suspension is highly enriched,
the possibility of some pars recta contamination in the MTAL tubule
suspension cannot be ruled out.
Na+-HCO3
cotransport shows adaptive regulation in certain pathophysiological
disorders, including metabolic acidosis or alkalosis. Functional
studies indicate that
Na+-HCO3
cotransport in the basolateral membrane of proximal tubule epithelial
cells is upregulated in metabolic acidosis and downregulated in
metabolic alkalosis (1). However, NBC-1 mRNA levels remained unchanged
after 4 days of acidosis, indicating that its upregulation in acidosis
is likely to be mediated by a posttranscriptional event, such as
phosphorylation or an increase in protein abundance similar to NHE-3
upregulation in acidosis (2). NBC-1 mRNA decreased by 35% in rats
placed on the HCO3 loading regimen.
The fact that animals did not show a high degree of alkalosis (plasma
[HCO3] = 23 vs. 27 mM)
indicates that inhibition of NBC-1-mediated
HCO3 reabsorption must occur, which
would cause increased renal excretion of
HCO3 by the kidney and attenuation of
alkalosis. NBC-1 mRNA did not change significantly in CDA, despite a
massive HCO3 load. The lack of
significant downregulation of NBC-1 might be due to the short interval
between induction of alkalosis and harvesting the tissue.
Alternatively, it has been shown that a decrease in glomerular
filtration rate accompanies CDA (10), which results in a reduced
delivery of HCO3 to the proximal
tubule and no increase in total filtered load. Hence, no greater demand
may be placed on the
Na+-HCO3
cotransporter in CDA than under normal conditions. It is worth
noting that CDA differs from other models of alkalosis (1) in
that depletion of Cl
causes a need to retain alternative anions, such as (and
in particular) HCO3, to prevent
volume contraction.
In conclusion, a rat NBC-1 cDNA clone was identified using a human EST
probe to screen a rat kidney cDNA library. Its distribution in various
tissues and nephron segments was studied. NBC-1 hybridizes to an mRNA
of ~8 kb and encodes a protein of 116 kDa (prior to any
posttranslational modification). The amino acid sequence is 96%
identical to human NBC-1, 87% identical to salamander NBC, and has
substantial homology to the AE family of bicarbonate transporters. It
is expressed in kidney, brain, heart, stomach, and colon. Under normal
conditions in the kidney, NBC-1 is most highly expressed in proximal
tubule, consistent with its role in vectorial transport of
HCO3 and acid-base homeostasis. mRNA
levels for NBC-1 were downregulated in
HCO3 loading and remained unchanged in
metabolic acidosis or chloride-depletion alkalosis.
| |
NOTE ADDED IN PROOF |
|---|
The Na+:HCO3 cotransporter
nucleotide and amino acid sequence reported in this study were released
by GenBank in November 1997 and are identical to those reported in
February 1998 by Romero et al. (M. F. Romero, P. Fong, U. V. Berger, M. A. Hediger, and W. F. Boron. Cloning and functional expression of rNBC,
an electrogenic Na+-HCO3
cotransporter from rat kidney. Am. J. Physiol. 274 (Renal Physiol. 43):F425-F432, 1998).
| |
ACKNOWLEDGEMENTS |
|---|
These studies were supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-46789 (to M. Soleimani) and DK-50594 (to G. E. Shull) and by a grant from Dialysis Clinic Incorporated (to M. Soleimani).
| |
FOOTNOTES |
|---|
Address for reprint requests: C. E. Burnham, Univ. of Cincinnati College of Medicine, Division of Nephrology and Hypertension, 231 Bethesda Ave., Cincinnati, OH 45267-0585.
Received 6 October 1997; accepted in final form 19 February 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Procedures
Results
Discussion
References
|
|---|
1.
Akiba, T.,
V. K. Rocco,
and
D. G. Warnock.
Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.
J. Clin. Invest.
80:
308-315,
1987.
2.
Ambühl, P. M.,
M. Amemiya,
M. Danczkay,
M. Lotscher,
B. Kaissling,
O. W. Moe,
P. A. Preisig,
and
R. J. Alpern.
Chronic metabolic acidosis increases NHE-3 protein abundance in rat kidney.
Am. J. Physiol.
271 (Renal Fluid Electrolyte Physiol. 40):
F917-F925,
1996
3.
Amlal, H.,
M. Paillard,
and
M. Bichara.
Cl-dependent NH+4 transport mechanisms in medullary thick ascending limb cells.
Am. J. Physiol.
267 (Cell Physiol. 36):
C1607-C1615,
1994
4.
Aronson, P. S.,
M. Soleimani,
and
S. M. Grassl.
Properties of the renal Na+-HCO3 cotransporter.
Semin. Nephrol.
11:
28-36,
1991[Medline].
5.
Boron, W. F.,
and
E. L. Boulpaep.
The electrogenic Na/HCO3 cotransporter.
Kidney Int.
36:
392-402,
1989[Medline].
6.
Burnham, C. E.,
H. Amlal,
Z. Wang,
G. E. Shull,
and
M. Soleimani.
Cloning and functional expression of a human kidney Na+:HCO3 cotransporter.
J. Biol. Chem.
272:
19111-19114,
1997
7.
Church, G. M.,
and
W. Gilbert.
Genomic sequencing.
Proc. Natl. Acad. Sci. USA
81:
1991-1995,
1984
8.
Fitz, J. C.,
M. Persico,
and
B. F. Scharschmidt.
Electrophysiological evidence for Na-coupled bicarbonate transport in cultured rat hepatocyte.
Am. J. Physiol.
256 (Gastrointest. Liver Physiol. 19):
G491-G500,
1989
9.
Galla, J. H.,
D. N. Bonduris,
and
R. G. Luke.
Correction of acute chloride-depletion alkalosis in the rat without volume expansion.
Am. J. Physiol.
244 (Renal Fluid Electrolyte Physiol. 13):
F217-F221,
1983.
10.
Galla, J. H.,
D. N. Bonduris,
P. W. Sanders,
and
R. G. Luke.
Volume independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat: evidence for mediation by tubuloglomerular feedback.
J. Clin. Invest.
74:
2002-2008,
1984.
11.
Good, D. W.
HCO3 absorption by Henle's loop.
Semin. Nephrol.
10:
132-139,
1990[Medline].
12.
Jabs, K.,
M. L. Zeidel,
and
P. Silva.
Prostaglandin E2 inhibits Na+-K+-ATPase activity in the inner medullary collecting duct.
Am. J. Physiol.
257 (Renal Fluid Electrolyte Physiol. 26):
F424-F430,
1989
13.
Krapf, R.,
and
R. J. Alpern.
Cell pH and transepithelial H/HCO3 transport in the renal proximal tubule.
J. Membr. Biol.
131:
1-10,
1993[Medline].
14.
Kudrycki, K. E.,
P. R. Newman,
and
G. E. Shull.
cDNA cloning and tissue distribution of mRNAs for two proteins that are related to the band 3 Cl/HCO3 exchanger.
J. Biol. Chem.
265:
462-471,
1990
15.
Lagadic-Gossmann, D.,
K. J. Buckler,
and
R. D. Vaughn-Jones.
Role of HCO3 in pH recovery from intracellular acidosis in the guinea-pig ventricular myocyte.
J. Physiol. (Lond.)
458:
361-384,
1992
16.
Levine, D. Z.,
D. Vandorpe,
and
M. Iacovitti.
Luminal chloride modulates rat distal tubule bidirectional bicarbonate flux in vivo.
J. Clin. Invest.
85:
1793-1798,
1990.
17.
Lux, S. E.,
K. M. John,
R. R. Kopito,
and
H. F. Lodish.
Cloning and characterization of band 3, the human erythrocyte anion-exchange protein (AE1).
Proc. Natl. Acad. Sci. USA
86:
9089-9093,
1989
18.
Mahnensmith, R. L.,
and
P. S. Aronson.
The plasma membrane sodium-hydrogen exchanger and its role physiological and pathophysiological processes.
Circ. Res.
56:
773-788,
1985
19.
Preisig, P. A.,
and
R. J. Alpern.
Basolateral membrane H-OH-HCO3 transport in the proximal tubule.
Am. J. Physiol.
256 (Renal Fluid Electrolyte Physiol. 25):
F751-F756,
1989
20.
Romero, M. F.,
M. A. Hediger,
E. L. Boulpaep,
and
W. F. Boron.
Expression cloning and characterization of a renal electrogenic Na+:HCO3 cotransporter.
Nature
387:
409-413,
1997[Medline].
21.
Shull, G. E.,
J. Greeb,
and
J. B. Lingrel.
Molecular cloning of three distinct forms of the Na+,K+-ATPase -subunit from rat brain.
Biochemistry
25:
8125-8132,
1986[Medline].
22.
Soleimani, M.,
and
P. S. Aronson.
Ionic mechanism of Na-HCO3 cotransport in rabbit renal basolateral membrane vesicles.
J. Biol. Chem.
264:
18302-18308,
1989
23.
Soleimani, M.,
G. Bizal,
Y. Hattabaugh,
P. S. Aronson,
and
J. Bergman.
Acute regulation of Na+:HCO3 cotransporter system in kidney proximal tubules.
In: Molecular and Cellular Mechanisms of H+ Transport, edited by B. H. Hirst. Berlin: Springer-Verlag, 1994.
24.
Soleimani, M.,
G. L. Bizal,
T. D. McKinney,
and
Y. J. Hattabaugh.
Effect of in vitro metabolic acidosis on luminal Na+/H+ exchange and basolateral Na+: HCO3 cotransport in rabbit kidney proximal tubules.
J. Clin. Invest.
90:
211-218,
1992.
25.
Soleimani, M.,
S. M. Grassl,
and
P. S. Aronson.
Stoichiometry of the Na+-HCO3 co-transporter in basolateral membrane vesicles isolated from rabbit renal cortex.
J. Clin. Invest.
79:
1276-1280,
1987.
26.
Soleimani, M.,
and
G. Singh.
Physiologic and molecular aspects of the Na+/H+ exchangers in health and disease processes.
J. Investig. Med.
43:
419-430,
1995[Medline].
27.
Wall, B. M.,
G. V. Byrum,
J. H. Galla,
and
R. G. Luke.
Importance of chloride for the correction of chronic metabolic alkalosis in the rat.
Am. J. Physiol.
253 (Renal Fluid Electrolyte Physiol. 22):
F1031-F1039,
1987
28.
Yoshitomi, K.,
B.-C. Burckhardt,
and
E. Fromter.
Rheogenic sodium-bicarbonate co-transport in the peritubular cell membrane of rat renal proximal tubule.
Pflügers Arch.
405:
360-366,
1985[Medline].
This article has been cited by other articles:
|
|
 |
|
  A. Brandes, O. Oehlke, A. Schumann, S. Heidrich, F. Thevenod, and E. Roussa Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2400 - R2411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, X. C. Sun, and J. A. Bonanno Role of NBC1 in apical and basolateral HCO3- permeabilities and transendothelial HCO3- fluxes in bovine corneal endothelium Am J Physiol Cell Physiol, March 1, 2005; 288(3): C739 - C746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Kim, T.-H. Kwon, B. M. Christensen, J. Nielsen, S. M. Wall, K. M. Madsen, J. Frokiaer, and S. Nielsen Altered expression of renal acid-base transporters in rats with lithium-induced NDI Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1244 - F1257. [Abstract] [Full Text]
|
|
|
|
|
|
H. Satoh, N. Moriyama, C. Hara, H. Yamada, S. Horita, M. Kunimi, K. Tsukamoto, N. Iso-o, J. Inatomi, H. Kawakami, et al. Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas Am J Physiol Cell Physiol, March 1, 2003; 284(3): C729 - C737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, Z. Wang, S. Barone, M. Petrovic, H. Amlal, L. Conforti, S. Petrovic, and M. Soleimani Expression of the Na+-HCO-3 cotransporter NBC4 in rat kidney and characterization of a novel NBC4 variant Am J Physiol Renal Physiol, January 1, 2003; 284(1): F41 - F50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Petrovic, Z. Wang, L. Ma, and M. Soleimani Regulation of the apical Cl--/HCO-3 exchanger pendrin in rat cortical collecting duct in metabolic acidosis Am J Physiol Renal Physiol, January 1, 2003; 284(1): F103 - F112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Baetz, R. S. Haworth, M. Avkiran, and D. Feuvray The ERK pathway regulates Na+-HCO3- cotransport activity in adult rat cardiomyocytes Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2102 - H2109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bourgeois, S. Masse, M. Paillard, and P. Houillier Basolateral membrane Cl--, Na+-, and K+-coupled base transport mechanisms in rat MTALH Am J Physiol Renal Physiol, April 1, 2002; 282(4): F655 - F668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. MAUNSBACH, H. VORUM, T.-H. KWON, S. NIELSEN, B. SIMONSEN, I. CHOI, B. M. SCHMITT, W. F. BORON, and C. AALKJæR Immunoelectron Microscopic Localization of the Electrogenic Na/HCO3 Cotransporter in Rat and Ambystoma Kidney J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2179 - 2189. [Abstract] [Full Text]
|
|
|
|
|
|
X. C. Sun, J. A. Bonanno, S. Jelamskii, and Q. Xie Expression and localization of Na+-HCO3- cotransporter in bovine corneal endothelium Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1648 - C1655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Amlal, K. Habo, and M. Soleimani Potassium deprivation upregulates expression of renal basolateral Na+-HCO3- cotransporter (NBC-1) Am J Physiol Renal Physiol, September 1, 2000; 279(3): F532 - F543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Bevensee, B. M. Schmitt, I. Choi, M. F. Romero, and W. F. Boron An electrogenic Na+-HCO-3 cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain Am J Physiol Cell Physiol, June 1, 2000; 278(6): C1200 - C1211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-H. Kwon, A. Pushkin, N. Abuladze, S. Nielsen, and I. Kurtz Immunoelectron microscopic localization of NBC3 sodium-bicarbonate cotransporter in rat kidney Am J Physiol Renal Physiol, February 1, 2000; 278(2): F327 - F336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pushkin, K.-P. Yip, I. Clark, N. Abuladze, T.-H. Kwon, S. Tsuruoka, G. J. Schwartz, S. Nielsen, and I. Kurtz NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase Am J Physiol Renal Physiol, December 1, 1999; 277(6): F974 - F981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pushkin, N. Abuladze, I. Lee, D. Newman, J. Hwang, and I. Kurtz Cloning, Tissue Distribution, Genomic Organization, and Functional Characterization of NBC3, a New Member of the Sodium Bicarbonate Cotransporter Family J. Biol. Chem., June 4, 1999; 274(23): 16569 - 16575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Amlal, C. E. Burnham, and M. Soleimani Characterization of Na+/HCO-3 cotransporter isoform NBC-3 Am J Physiol Renal Physiol, June 1, 1999; 276(6): F903 - F913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shumaker, H. Amlal, R. Frizzell, C. D. Ulrich II, and M. Soleimani CFTR drives Na+-nHCO-3 cotransport in pancreatic duct cells: a basis for defective HCO-3 secretion in CF Am J Physiol Cell Physiol, January 1, 1999; 276(1): C16 - C25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-H. Kwon, C. Fulton, W. Wang, I. Kurtz, J. Frokiar, C. Aalkjar, and S. Nielsen Chronic metabolic acidosis upregulates rat kidney Na-HCO3- cotransporters NBCn1 and NBC3 but not NBC1 Am J Physiol Renal Physiol, February 1, 2002; 282(2): F341 - F351. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||
