1 Department of Pharmacology, Medical College of Ohio, Toledo, Ohio 43614; and 2 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871, Russia
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ABSTRACT |
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The molecular basis of active ion
transport in secretory glands such as the prostate is not well
characterized. Rat nongastric H-K-ATPase is expressed at high
levels in distal colon surface cell apical membranes and thus is
referred to as "colonic." Here we show that the ATPase is expressed
in rodent prostate complex in a lobe-specific manner. RT-PCR and
Western blot analyses indicate that rat nongastric H-K-ATPase
-subunit (
ng) mRNA and protein are present in
coagulating gland (anterior prostate) and lateral and dorsal
prostate and absent from ventral lobe, whereas Na-K-ATPase
-subunit is present in all lobes. RT-PCR analysis shows that Na-K-ATPase
4 and
3 and gastric
H-K-ATPase
-subunit are not present in significant amounts in all
prostate lobes. Relatively low levels of Na-K-ATPase
2
were found in lateral, dorsal, and anterior lobes.
ng
protein expression is anteriodorsolateral: highest in coagulating
gland, somewhat lower in dorsal lobe, and even lower in lateral lobe.
Na-K-ATPase protein abundance has the reverse order: expression in
ventral lobe is higher than in coagulating gland.
ng
protein abundance is higher in coagulating gland than distal colon
membranes. Immunohistochemistry shows that in rat and mouse coagulating
gland epithelium
ng protein has an apical polarization
and Na-K-ATPase
1 is localized in basolateral membranes.
The presence of nongastric H-K-ATPase in rodent prostate apical
membranes may indicate its involvement in potassium concentration
regulation in secretions of these glands.
ATP1AL1; ATP12A; hydrogen-potassium-adenosinetriphosphatase; sodium-potassium-adenosinetriphosphatase; X-potassium-adenosinetriphosphatase; male accessory glands; potassium transport
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INTRODUCTION |
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THE FAMILY OF
X-K-ATPASES is responsible for inward potassium transport
in exchange for sodium (Na-K-ATPase) or protons (gastric and nongastric
H-K- ATPases). Mammalian X-K-ATPases consist of a catalytic
-subunits of ~110 kDa for which six genes have been identified and
a glycosylated
-subunit of ~35 kDa for which five genes are known
(6, 25, 27, 45). Almost all tissues have Na-K-ATPase
1- and
1-subunits (especially abundant in
kidney and brain), whereas other X-K-ATPase isoforms are restricted to particular tissues and cell types. The gastric H-K-ATPase
- and
-subunits are specific for parietal cells of the stomach mucosa, X-K-ATPase
muscle (
m) for striated
muscle, and Na-K-ATPase
4 for male germ cells;
Na-K-ATPase
2,
3, and
2 are characteristic for excitable tissues (muscle,
brain, retina, etc). Na-K-ATPase
3 has a
peculiar pattern of expression: its mRNA is abundant in testis, brain,
and adrenals, whereas significant amounts of the protein have been
detected in lung, testis, and liver (6).
The -subunit of the nongastric ouabain-sensitive H-K-ATPase
(
ng), which was cloned from rat colon (17)
and thus is also referred to as "colonic" H-K-ATPase (also
HK
2-6; Ref. 27), is encoded by the
gene ATP12A (alternative name ATP1AL1).
Full-length mRNA sequences for the rat (17), human
(25), guinea pig (3), rabbit (8,
21), and toad (29) enzymes and partial sequences for the mouse and dog (46) enzymes are known. Noncanonical
transcripts that include parts of the first intron from rat
(30) and rabbit (8) genes have also been reported.
Although the role of the nongastric H-K-ATPase in H+ secretion and K+ reabsorption under normal conditions has not yet been demonstrated directly, its adaptive regulation to pathophysiological conditions such as potassium depletion, NaCl deficiency, and renal acidosis argues in favor of an important role of this ion pump in disease states associated with dysfunctions of electrolyte homeostasis (for review, see Refs. 53 and 56).
Catalytic properties of the rat, guinea pig, and human nongastric
H-K-ATPases have been studied extensively by several groups using
different heterologous expression systems [Xenopus oocytes (12, 14-16, 22, 29, 41), kidney cell line HEK
(3, 23, 24, 30, 51), and insect cells (1,
35)], different -subunits [gastric H-K-ATPase
-subunit
(1, 23, 24, 41),
1 (12, 14-16),
3 (51), all known
X-K-ATPase
-subunits (22), and without a
-subunit
partner (35)] and different methods of functional evaluation (86Rb uptake, measurements of intra- and
extracellular ions, and ATP-hydrolyzing activity). As a result
of these different experimental approaches, there is currently no
consensus on the catalytic properties of the enzyme. It has been
characterized either as ouabain-sensitive H+-K+-ATPase (3, 12, 16, 22, 23,
41) or ouabain-insensitive K-ATPase (51). Its
function may not be limited to H+/K+ exchange
but might include transport of Na+ (15, 24)
and NH
The initial studies on rat ATP12A by Crowson and Shull (17) demonstrated that the gene has a high level of expression in rat distal colon and a lower level in kidney, uterus, and forestomach, whereas the human gene is expressed in skin, kidney, and brain (25, 42). Later studies revealed more information on the cell type-specific expression and regulation of the gene. In mammalian kidney, this ATPase was detected in distal parts of the nephron (20, 21, 32, 36, 57) and is increased by stresses such as ischemia-reperfusion (58) or dietary potassium depletion (11, 18, 21, 50). In rat colon this ATPase is specific for surface cells (28, 47) and undergoes upregulation by dietary or hormonal disturbances of ion homeostasis (13, 50). Under some pathological conditions [chronic diarrhea in Na/H exchanger (NHE)3-deficient mice], its expression in distal colon is also elevated and becomes detectable in proximal colon (52). Ablation of the ATPase by gene targeting results in an increased fecal potassium loss under potassium-deprived conditions (38).
Because the cellular location of the ATPase in distal colon and kidney
was found to be the apical membranes (20, 32, 47, 57), it
is usually thought to be a specific apical marker in some
ion-transporting epithelia. However, when heterologously expressed, the
human ng is localized in renal epithelial cells differentially: predominantly apically in the MDCK cell line and laterally in the LLC-PK1 cell line (48).
Moreover, at least in some tissues like uterus, the ATPase transcripts
were detected not in the luminal epithelium but instead in "blood
vessel-rich areas" (28).
Because the initial studies on the tissue-specific expression of the
human and rat genes (17, 25) suggested that they may
encode different isoforms (27, 30, 52), in a previous paper (46) we described a broader screening of the
expression in different tissues of several mammalian species (mouse,
rat, rabbit, human, and dog) by RT-PCR. It was demonstrated that the tissue specificity of the expression in these species is almost identical. Thus these mammalian genes have not only structural but also
functional homology (25, 27, 46, 54). Another interesting
observation was that a significant level of expression was detected in
some rat male accessory organs, the preputial gland and a part of the
prostate complexthe coagulating gland (46).
Studies on X-K-ATPases in prostate are very limited despite the
significant biomedical importance of this organ, and most of these
studies have been carried out using only the ventral lobe of the rat
prostate (2, 19, 59). Also, the coagulating gland is a
convenient model for studies of apocrine secretion (4).
Thus we decided to investigate the expression of ng in rodent prostate in more detail compared with Na-K-ATPase.
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MATERIALS AND METHODS |
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RT-PCR and cDNA cloning.
Primer sequences for the detection of rat and mouse ng
transcripts were described previously (46). For
transcripts of X-K-ATPase
-subunits the following primer pairs were
used: FR123 (gaagctcatcatygtggagggctg) and BR123
(kkggctgcctcttcatgatgtc) for
1,
2, and
3; AF1 (yctytctctsatccttgagtacac) and AB1
(gttagcctgaaacactgccctgt) for
1; AF2
(gayctggaggacagctatggaca) and AB2 (aggrtaccgccgcaggatgagc) for
2; AF3 (accagctatccatccatgagac) and AB3
(ggagggtcgatcatggacatga) for
3; A4MRF
(acaactttgcctccattgtgac) and A4MRB (ttcatgccctgcttgaagagt) for
4; and GAMRHF (ycagattggtgccattcagtc) and GAMRHB
(gyttccggatctcatcatagac) for gastric H-K-ATPase
-subunit. Conditions of RT-PCR were essentially as described previously (46) with the exception that the annealing temperature for
1 primers was set at 50°C. Agarose gels were imaged
with the help of a Typhoon 8600 laser scanner (Amersham Pharmacia,
Piscataway, NJ).
Antibodies. Recombinant protein expression in Escherichia coli, purification by immobilized metal affinity chromatography, and immunization of rabbits were achieved essentially as described previously (31). Affinity purification of antibodies was performed with the antigens absorbed on polyvinylidene difluoride (PVDF) membrane according to the method of Rucklidge et al. (49).
Mouse monoclonal antibodyPreparation of membranes.
Sprague-Dawley rats weighing 200-300 g were killed by
decapitation. Tissue samples were frozen in liquid nitrogen, powdered with a hammer, and homogenized with a Polytron homogenizer at 12,000 rpm for 1 min in buffer A [10 mM HEPES-Na, 1 M KCl, 5 mM Na-EDTA, 0.25 M sucrose, protease inhibitor cocktail (P2714, Sigma), 100 µM phenylmethylsulfonyl fluoride (PMSF), 0.1% methanol, pH 7.0]. The homogenate was centrifuged at 9,000 g for 20 min,
and the microsomes were pelleted at 150,000 g for 30 min.
The membranes were washed with buffer A without KCl,
resuspended in a small volume of the buffer, freed from remaining
debris by centrifugation for 5 min at 4,000 g, and stored at
70°C.
Western blotting.
Membranes were dissolved in SDS sample loading buffer
(34), and the protein concentration was measured by a
modification of the Bradford procedure that includes coprecipitation of
proteins with calcium phosphate (43). Proteins (10 µg/well) were electrophoresed in 8% polyacrylamide gels and blotted
onto PVDF membrane (Amersham Pharmacia). The membrane was washed in
methanol and stained in 50% methanol-1% acetic acid-0.03% Coomassie
brilliant blue G-250 followed by washes with 50% methanol. The
membrane was then cut, destained in methanol, washed in 50% methanol
followed by incubation in 50 mM Tris-(pH 6.8)-100 mM
mercaptoethanol-2% SDS for 15 min at room temperature, washed in
Tris-buffered saline (TBS), and blocked in TBS containing 5% nonfat
milk. The membrane was consequently incubated with the
affinity-purified rabbit antibodies and then either with
peroxidase-conjugated anti-rabbit antibodies (Amersham Pharmacia) or,
for maximal sensitivity, subsequently with biotin-conjugated anti-rabbit antibodies (Amersham Pharmacia) and streptavidin-peroxidase (S9420, Sigma) for 1 h each with thorough washes in TBS containing 0.1% Tween 20 between incubations. The immunoblots were visualized with a chemiluminescent substrate (ECL+Plus, Amersham Pharmacia). For
negative controls, the same reagents were used except that affinity-purified rabbit antibodies against a nonrelated His-tagged protein (45) were substituted for anti-ng
antibodies. Molecular mass standards were the 10-kDa protein ladder
(Life Technologies, Rockville, MD). Densitometry was performed with a
Bio-Rad Model GS-690 imaging densitometer (Bio-Rad Laboratories,
Hercules, CA).
Immunohistochemistry. Tissues were frozen in isopentane-liquid nitrogen and cut at 15-µm thickness. Sections were fixed with 5% paraformaldehyde in PBS, dehydrated in graded ethanols, and air dried. The sections were treated for 1 h with 1% hydrogen peroxide in PBS followed by PBS containing 5% normal porcine serum, 0.2% Triton X-100, 0.02% saponin, 0.05% sodium azide, and 50 mM glycine pH 7.5 at room temperature for 1 h and then incubated with the primary antibodies in PBS containing 1% pig serum overnight. The sections were washed in PBS and developed using Vectastain ABC anti-rabbit kit (Vector Laboratories, Burlingame, CA) and NovaRED peroxidase substrate (Vector Laboratories).
For labeling with anti-Na-K-ATPase antibodies (both rabbit anti-KETYY and mouse monoclonal anti- ![]() |
RESULTS |
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Analysis of mouse ATP12A gene.
We (46) previously determined the partial sequence of the
cDNA encoding mouse ng and showed it to have a high
level of sequence identity with the homologous rat protein
(17). Using these and other sequence data as well as the
known exon-intron structure of the human ATP12A gene
(54), we have identified the corresponding mouse gene in
genomic clone RP23-178B24 (Birren B, Linton L, Nusbaum C, and
Lander E; GenBank accession no. AC021630). The deduced sequence of the
mouse cDNA coding region exhibits 94.4% identity with that of the rat
cDNA. The encoded protein consists of 1,035 amino acid residues and has
a molecular mass of 114.7 kDa (Fig. 1).
Mouse and rat protein sequences exhibit 95.9% identity (only 9 of 39 replacements are not isofunctional). The level of sequence homology
between the mouse and related proteins from guinea pig, rabbit, and
human is slightly lower, being 88%, 86.9%, and 86.3%, respectively.
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Production of fragments of nongastric H-K-ATPase and generation of
specific antibodies.
We previously described (31) the preparation of poly- and
monoclonal antibodies specific to the NH2-terminal fragment
of human ng. This fragment was chosen because its
sequence is the least homologous to other isoforms of X-K-ATPase
including the ubiquitous
1. Indeed, these antibodies
showed no reactivity with Na-K-ATPase purified from kidney (results not
shown). However, the advantage of the sequence dissimilarity of the
NH2 terminus became a drawback when we attempted to detect
animal nongastric H-K-ATPases. No reliable immunodetection was achieved
in Western blotting of rat or rabbit distal colon microsomes with these
antibodies (data not shown). To circumvent this problem, we raised
antibodies against the rat NH2 terminus. The cDNA fragment
coding for the rat NH2-terminal fragment (coordinates
13-102) was cloned into an expression vector with the
NH2-terminal hexahistidine tag using RT-PCR from rat distal
colon cDNA.
Immunodetection of nongastric H-K-ATPase protein in membranes from
various rat tissues.
Using these specific antibodies we analyzed several rat tissues, chosen
according to the previously described RT-PCR screening (46), for the presence of ng.
Immunoblotting analyses of crude microsome proteins from these rat
tissues are represented in Fig. 2. A
strong band corresponding to an apparent molecular mass of ~108 kDa
was observed in the distal colon (Fig. 2), in accordance with the
results of other laboratories (20, 35, 47).
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Analysis of lobe-specific expression of nongastric H-K-ATPase and
Na-K-ATPase -subunit in rat prostate complex.
The dramatic difference in the expression of
ng in
coagulating gland and ventral prostate (Fig. 2) persuaded us to
investigate the lobe specificity of
ng expression in
more detail as well as to obtain some information on the lobe
specificity of expression of other known X-K-ATPase isoforms.
Additionally, ampullary gland was also included in some experiments
because this organ had not been studied before.
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Immunohistochemical localization of nongastric H-K-ATPase protein
in rodent coagulating gland.
Immunohistochemical localization of ng protein is
demonstrated in Fig. 6 with both
immunoperoxidase (Fig. 6A) and immunofluorescence (Fig.
6B) techniques. Affinity-purified antibodies against the NH2-terminal fragment of rat
ng produce a
strong labeling, which is confined to the luminal surface of epithelial
cells. Antibodies directed against a nonrelated hexahistidine-tagged
recombinant protein (
m; Ref. 45) did not
produce any significant labeling, and neutralization of the primary
antibodies with the original antigen eliminates the specific labeling
(results not shown). The fact that the labeling was strictly confined
to the lumen-exposed surface suggests that the nongastric H-K-ATPase is
localized to the apical membranes of the epithelial cells and is absent
from their basolateral membranes.
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DISCUSSION |
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Expression of novel genes in tissues like small specialized
secretory glands are not usually well studied. However, the
physiological significance of paralogous genes and protein isoforms
cannot be fully understood without exhaustive knowledge of their
tissue-specific expression. The present work illustrates this by the
finding that rat ng is expressed in several lobes of the
prostate at a higher level than in distal colon, the tissue that
provided one of the names of H-K-ATPase.
An interesting fact is that the ATPase is expressed in the rat prostate
in a lobe-specific manner, being virtually absent in the ventral part
and present in the lateral and dorsal lobes and the coagulating gland
(anterior prostate), an expression pattern that can be called
anteriodorsolateral. This fact by itself is not unusualother proteins
are known to be expressed lobe-specifically, for example,
-microseminoprotein is specific for lateral prostate (33). However, to our knowledge this is the first report
of the lobe-specific expression of a P-type ATPase.
Immunohistochemical localization of the ATPase in mouse and rat
coagulating glands demonstrates that the ATPase is strictly confined to
the lumen-exposed surface of the epithelium, and this means that the
ATPase has apical polarization in rodent prostate epithelial cells. In
contrast, 1-subunit of Na-K-ATPase was detected only in
basolateral membranes of the coagulating gland. This is in line with
observations of localization of the ATPases in rat distal colon
(35, 47) and strengthens the view that protein sorting
machinery destines Na-K-ATPase to basolateral and H-K-ATPase (both
gastric and nongastric) to apical membrane compartments. Basolateral
polarization of Na-K-ATPase in rat prostate has already been observed
(39, 44), unfortunately without indication of the lobe
used. However, Mobasheri et al. (40) recently reported that in human prostate epithelium, in contrast to the rat, Na-K-ATPase is present in both apical and lateral membranes. Although apical Na-K-ATPase was also found in some other epithelia, for example, in choroid plexus (37), the observation of
species-specific differences in prostatic Na-K-ATPase
polarization is intriguing.
The function of H-K-ATPase in rodent prostate is not easy to understand because the available data on ion composition on its secretion are rather limited (7). To the best of our knowledge, there are no data on the ion content in the secretions of the rat or mouse coagulating gland. However, Chow et al. (10) have extensively studied the secretions in these glands in the golden hamster. These studies showed that the ionic composition of the secretions from different parts of the prostate varies significantly. For example, the potassium concentration was 2.59 meq/l for the coagulating gland, 21.44 meq/l for the dorsolateral prostate, and 103.2 meq/l for the ventral prostate. Assuming that these values are also true in other rodent species and that the golden hamster has the same lobe-specific expression of nongastric H-K-ATPase, it would be reasonable to predict that the potassium concentration in the secretions is inversely related to the content of nongastric H-K-ATPase. This suggests that the function of prostatic H-K-ATPase is to take up potassium from the luminal fluids, thus maintaining the low potassium concentration. Because this enzyme performs H+/K+ exchange, its function could also result not only in the decrease of potassium in the extracellular fluid but also in its acidification. This luminal acidification may also be accomplished by V-type H+-ATPase. Interestingly, the pattern of this enzyme's cellular expression was shown to be different in different lobes of rat prostate. It was located mostly intracellularly in coagulating gland and ventral prostate but in both apical and basolateral membranes of the lateral prostate (26). Clearly, every lobe of the prostate has a very specific set of ion transporters.
Nongastric H-K-ATPase is thought to be involved in maintenance of electrolyte homeostasis through K+ absorption and proton secretion in kidney and colon, especially in disease processes including ionic and acid-base disorders. The physiological importance of the differences in potassium concentration in secretions from different prostate lobes (10) is currently unknown, and it is especially difficult to examine because during copulation these secretions are mixed together (also with semen and fluids from seminal vesicles and uterus). This mixing leads to the formation of the so-called copulatory plug for which secretions of the coagulating gland are especially important (9), being the major source of the protein-cross-linking enzyme transglutaminase. At present, it is hardly possible to suggest a satisfactory explanation for the differences in the potassium concentration in secretions of different lobes (10). However, we can suggest that either the activity of some enzymes is regulated by potassium (for example, they might be inactive in the low-potassium fluid of the coagulating gland and be activated after the mixing of the secretions during coitus) or the prostate epithelium may use the K+ gradient for secondary transport processes. Whatever the exact relevance of the H+/K+ exchange in some parts of the rodent prostate may be, it is reasonable to speculate that the function of nongastric H-K-ATPase in these male accessory glands is important for normal formation of the copulatory plug.
In conclusion, we have found that ng is highly expressed
in rodent prostate epithelium and is polarized to the apical membranes. Because the relative content of nongastric H-K-ATPase is higher in the
coagulating gland than in distal colon (traditional tissues for the
studies on the enzyme) whereas the content of Na-K-ATPase is lower, the
coagulating gland may be a convenient source for isolation and further
characterization of the structure and the function of nongastric
H-K-ATPase.
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ACKNOWLEDGEMENTS |
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We are grateful to Dr. Jack Kyte (University of California, San Diego, CA.) for the gift of anti-Na-K-ATPase polyclonal antibodies and Drs. Amir Askari, Andrew D. Beavis, and Sonia Najjar for valuable comments on the manuscript.
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FOOTNOTES |
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This work was supported by National Institutes of Health Grants HL-36573 and GM-54997 and by Russian Foundation for Basic Research Grants 00-04-48153 and 98-04-48408.
Address for reprint requests and other correspondence: N. N. Modyanov, Dept. of Pharmacology, Medical College of Ohio, 3035 Arlington Ave., Toledo, OH 43614 (E-mail: nmodyanov{at}mco.edu).
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.
10.1152/ajpcell.00258.2001
Received 11 June 2001; accepted in final form 7 December 2001.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Adams, G,
Tillekeratne M,
Yu C,
Pestov NB,
and
Modyanov NN.
Catalytic function of nongastric H,K-ATPase expressed in Sf-21 insect cells.
Biochemistry
40:
5765-5776,
2001[ISI][Medline].
2.
Ahmed, K,
and
Williams-Ashman HG.
Studies on the microsomal sodium-plus potassium ion-stimulated adenosine triphosphatase systems in rat ventral prostate.
Biochem J
113:
829-836,
1969[ISI][Medline].
3.
Asano, S,
Hoshina S,
Nakaie Y,
Watanabe T,
Sato M,
Suzuki Y,
and
Takeguchi N.
Functional expression of putative H+-K+-ATPase from guinea pig distal colon.
Am J Physiol Cell Physiol
275:
C669-C674,
1998[Abstract].
4.
Aumuller, G,
Wilhelm B,
and
Seitz J.
Apocrine secretionfact or artifact?
Anat Anz
181:
437-446,
1999[Medline].
5.
Bayer, R.
Topological disposition of the sequences -QRKIVE- and -KETYY in native (Na+ + K+)-ATPase.
Biochemistry
29:
2251-2256,
1990[ISI][Medline].
6.
Blanco, G,
and
Mercer B.
Isozymes of the Na,K-ATPase: heterogeneity in structure, diversity in function.
Am J Physiol Renal Physiol
275:
F633-F650,
1998
7.
Brooks, DE.
Biochemistry of the male accessory glands.
In: Marshall's Physiology of Reproduction, edited by Lammins GE.. Edinburgh, UK: Churchill Livingston, 1990, vol. 2, p. 569-690.
8.
Campbell, WG,
Weiner ID,
Wingo CS,
and
Cain BD.
H-K-ATPase in the RCCT-28A rabbit cortical collecting duct cell line.
Am J Physiol Renal Physiol
276:
F237-F245,
1999
9.
Carballada, R,
and
Esponda P.
Role of fluid from seminal vesicles and coagulating glands in sperm transport into the uterus and fertility in rats.
J Reprod Fertil
95:
639-648,
1992[Abstract].
10.
Chow, PH,
Chan CW,
and
Cheng LYL
Contents of fructose, citric acid, acid phosphatase, proteins and electrolytes in secretions of the accessory sex glands of the male golden hamster.
Int J Androl
16:
41-45,
1992[ISI].
11.
Codina, J,
Delmas-Mata JT,
and
DuBose TD, Jr.
Expression of HK2 protein is increased selectively in renal medulla by chronic hypokalemia.
Am J Physiol Renal Physiol
275:
F433-F440,
1998
12.
Codina, J,
Kone BC,
Delmas-Mata JT,
and
DuBose TD, Jr.
Functional expression of the colonic H+,K+-ATPase -subunit. Pharmacological properties and assembly with X+,K+-ATPase
-subunits.
J Biol Chem
271:
29759-29763,
1996
13.
Codina, J,
Pressley TA,
and
DuBose TD, Jr.
Effect of chronic hypokalemia on H+-K+-ATPase expression in rat colon.
Am J Physiol Renal Physiol
272:
F22-F30,
1997
14.
Cougnon, M,
Bouyer P,
Jaisser F,
Edelman A,
and
Planelles G.
Ammonium transport by the colonic H+-K+- ATPase expressed in Xenopus oocytes.
Am J Physiol Cell Physiol
277:
C280-C287,
1999
15.
Cougnon, M,
Bouyer P,
Planelles G,
and
Jaisser F.
Does the colonic H,K-ATPase also act as an Na,K-ATPase?
Proc Natl Acad Sci USA
95:
6516-6520,
1998
16.
Cougnon, M,
Planelles G,
Crowson MS,
Shull GE,
Rossier BC,
and
Jaisser F.
The rat distal colon P-ATPase -subunit encodes a ouabain-sensitive H+,K+-ATPase.
J Biol Chem
271:
7277-7280,
1996
17.
Crowson, MS,
and
Shull GE.
Isolation and characterization of a cDNA encoding the putative distal colon H+,K+-ATPase. Similarity of deduced amino acid sequence to gastric H+,K+-ATPase and Na+,K+-ATPase and mRNA expression in distal colon, kidney, and uterus.
J Biol Chem
267:
13740-13748,
1992
18.
DuBose, TD, Jr,
Codina J,
Burges A,
and
Pressley TA.
Regulation of H+-K+-ATPase expression in kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
269:
F500-F507,
1995
19.
Farnsworth, WE.
Prostate plasma membrane receptor: a hypothesis.
Prostate
19:
329-352,
1991[ISI][Medline].
20.
Fejes-Tóth, G,
and
Náray-Fejes-Tóth A.
Immunohistochemical localization of colonic H-K-ATPase to the apical membrane of connecting tubule cells.
Am J Physiol Renal Physiol
281:
F318-F325,
2001
21.
Fejes-Tóth, G,
Náray-Fejes-Tóth A,
and
Velazquez H.
Intrarenal distribution of the colonic H,K-ATPase mRNA in rabbit.
Kidney Int
56:
1029-1036,
1999[ISI][Medline].
22.
Geering, K,
Crambert G,
Yu C,
Korneenko TV,
Pestov NB,
and
Modyanov NN.
Intersubunit interactions in human X-K-ATPases: role of membrane domains M9 and M10 in the assembly process and association efficiency of human, nongastric H,K-ATPase -subunits (ATP1al1) with known
-subunits.
Biochemistry
39:
12688-12698,
2000[ISI][Medline].
23.
Grishin, AV,
Bevensee MO,
Modyanov NN,
Rajendran V,
Boron WF,
and
Caplan MJ.
Functional expression of the cDNA encoded by the human ATP1AL1 gene.
Am J Physiol Renal Fluid Electrolyte Physiol
271:
F539-F551,
1996
24.
Grishin, AV,
and
Caplan MJ.
ATP1AL1, a member of the nongastric H,K-ATPase family, functions as a sodium pump.
J Biol Chem
273:
27772-27778,
1998
25.
Grishin, AV,
Sverdlov VE,
Kostina MB,
and
Modyanov NN.
Cloning and characterization of the entire cDNA encoded by ATP1AL1a member of the human Na,K/H,K-ATPase gene family.
FEBS Lett
349:
144-150,
1994[ISI][Medline].
26.
Herak-Kramberger, CM,
Breton S,
Brown D,
Kraus O,
and
Sabolic I.
Distribution of the vacuolar H+ ATPase along the rat and human male reproductive tract.
Biol Reprod
64:
1699-1707,
2001
27.
Jaisser, F,
and
Beggah AT.
The nongastric H+-K+-ATPases: molecular and functional properties.
Am J Physiol Renal Physiol
276:
F812-F824,
1999
28.
Jaisser, F,
Coutry N,
Farman N,
Binder HJ,
and
Rossier BC.
A putative H+-K+-ATPase is selectively expressed in surface epithelial cells of rat distal colon.
Am J Physiol Cell Physiol
265:
C1080-C1089,
1993
29.
Jaisser, FN,
Horisberger K,
Geering K,
and
Rossier BC.
Mechanisms of urinary K+ and H+ excretion: primary structure and functional expression of a novel H,K-ATPase.
J Cell Biol
123:
1421-1429,
1993[Abstract].
30.
Kone, BC,
and
Higham SC.
A novel N-terminal splice variant of the rat H+-K+-ATPase 2 subunit. Cloning, functional expression, and renal adaptive response to chronic hypokalemia.
J Biol Chem
273:
2543-2552,
1998
31.
Korneenko, TV,
Pestov NB,
Egorov MB,
Ivanova MV,
Kostina MB,
and
Shakhparonov MI.
Monoclonal antibodies to the -subunit of the putative human H+,K+-ATPase encoded by the atp1al1 gene.
Bioorg Khim
23:
800-804,
1997[ISI][Medline].
32.
Kraut, JA,
Helander KG,
Helander HF,
Iroezi ND,
Marcus EA,
and
Sachs G.
Detection and localization of H+-K+-ATPase isoforms in human kidney.
Am J Physiol Renal Physiol
281:
F763-F768,
2001
33.
Kwong, J,
Xuan JW,
Choi HL,
Chan PSF,
and
Chan FL.
PSP94 (or -microseminoprotein) is a secretory protein specifically expressed and synthesized in the lateral lobe of the rat prostate.
Prostate
42:
219-229,
2000[ISI][Medline].
34.
Laemmli, UK.
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
Nature
227:
680-685,
1970[ISI][Medline].
35.
Lee, J,
Rajendran VM,
Mann AS,
Kashgarian M,
and
Binder HJ.
Functional expression and segmental localization of rat colonic K-adenosine triphosphatase.
J Clin Invest
96:
2002-2008,
1995[ISI][Medline].
36.
Marsy, S,
Elalouf JM,
and
Doucet A.
Quantitative RT-PCR analysis of mRNAs encoding a colonic putative H, K-ATPase subunit along the rat nephron: effect of K+ depletion.
Pflügers Arch
432:
494-500,
1996[ISI][Medline].
37.
Masuzawa, T,
Ohta T,
Kawamura M,
Nakahara N,
and
Sato F.
Immunohistochemical localization of Na+, K+-ATPase in the choroid plexus.
Brain Res
302:
357-362,
1984[ISI][Medline].
38.
Meneton, P,
Schultheis PJ,
Greeb J,
Nieman ML,
Liu LH,
Clarke LL,
Duffy JJ,
Doetschman T,
Lorenz JN,
and
Shull GE.
Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice.
J Clin Invest
101:
536-542,
1998
39.
Mobasheri, A,
Avila J,
Cozar-Castellano I,
Brownleader MD,
Trevan M,
Francis MJ,
Lamb JF,
and
Martín-Vasallo P.
Na+,K+-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions.
Biosci Rep
20:
51-91,
2000[ISI][Medline].
40.
Mobasheri, D,
Oukrif D,
Dawodu SP,
Sinha M,
Greenwell P,
Stewart D,
Djamgoz MBA,
Foster CS,
Martín-Vasallo P,
and
Mobasheri R.
Isoforms of Na+,K+-ATPase in human prostate; specificity of expression and apical membrane polarization.
Histol Histopathol
16:
141-154,
2001[ISI][Medline].
41.
Modyanov, NN,
Mathews PM,
Grishin AV,
Beguin P,
Beggah AT,
Rossier BC,
Horisberger JD,
and
Geering K.
Human ATP1AL1 gene encodes a ouabain-sensitive H-K-ATPase.
Am J Physiol Cell Physiol
269:
C992-C997,
1995
42.
Modyanov, NN,
Petrukhin KE,
Sverdlov VE,
Grishin AV,
Orlova MY,
Kostina MB,
Makarevich OI,
Broude NE,
Monastyrskaya GS,
and
Sverdlov ED.
The family of human Na,K-ATPase genes. ATP1AL1 gene is transcriptionally competent and probably encodes the related ion transport ATPase.
FEBS Lett
278:
91-94,
1991[ISI][Medline].
43.
Pande, SV,
and
Murthy MS.
A modified micro-Bradford procedure for elimination of interference from sodium dodecyl sulfate, other detergents, and lipids.
Anal Biochem
220:
424-426,
1994[ISI][Medline].
44.
Papanicolau, S,
Kajee R,
Martín-Vasallo P,
Djamgoz MBA,
and
Mobasheri A.
Isoforms of Na+,K+-ATPase in normal rat prostate: immunohistochemical evidence for expression of 1,
1,
2 and
3 (Abstract).
J Physiol (Lond)
525:
24P,
2000.
45.
Pestov, NB,
Korneenko TV,
Zhao H,
Adams G,
Shakhparonov MI,
and
Modyanov NN.
Immunochemical demonstration of a novel -subunit isoform of X-K-ATPase in human skeletal muscle.
Biochem Biophys Res Commun
277:
430-435,
2000[ISI][Medline].
46.
Pestov, NB,
Romanova LG,
Korneenko TV,
Egorov MV,
Kostina MB,
Sverdlov VE,
Askari A,
Shakhparonov MI,
and
Modyanov NN.
Ouabain-sensitive H,K-ATPase: tissue-specific expression of the mammalian genes encoding the catalytic -subunit.
FEBS Lett
440:
320-324,
1998[ISI][Medline].
47.
Rajendran, VM,
Singh SK,
Geibel J,
and
Binder HJ.
Differential localization of colonic H+-K+-ATPase isoforms in surface and crypt cells.
Am J Physiol Gastrointest Liver Physiol
274:
G424-G429,
1998
48.
Reinhardt, J,
Grishin AV,
Oberleithner H,
and
Caplan MJ.
Differential localization of human nongastric H+-K+-ATPase ATP1AL1 in polarized renal epithelial cells.
Am J Physiol Renal Physiol
279:
F417-F425,
2000
49.
Rucklidge, GJ,
Milne G,
Chaudhry SM,
and
Robins SP.
Preparation of biotinylated, affinity-purified antibodies for enzyme-linked immunoassays using blotting membrane as an antigen support.
Anal Biochem
243:
158-164,
1996[ISI][Medline].
50.
Sangan, P,
Rajendran VM,
Mann AS,
Kashgarian M,
and
Binder HJ.
Regulation of colonic H-K-ATPase in large intestine and kidney by dietary Na depletion and dietary K depletion.
Am J Physiol Cell Physiol
272:
C685-C696,
1997
51.
Sangan, P,
Thevananther S,
Sangan S,
Rajendran VM,
and
Binder HJ.
Colonic H-K-ATPase - and
-subunits express ouabain-insensitive H-K-ATPase.
Am J Physiol Cell Physiol
278:
C182-C189,
2000
52.
Schultheis, PJ,
Clarke LL,
Meneton P,
Miller ML,
Soleimani M,
Gawenis LR,
Riddle TM,
Duffy JJ,
Doetschman T,
Wang T,
Giebisch G,
Aronson PS,
Lorenz JN,
and
Shull GE.
Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger.
Nat Genet
19:
282-285,
1998[ISI][Medline].
53.
Silver, RB,
and
Soleimani M.
H+-K+-ATPases: regulation and role in pathophysiological states.
Am J Physiol Renal Physiol
276:
F799-F811,
1999
54.
Sverdlov, VE,
Kostina MB,
and
Modyanov NN.
Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase.
Genomics
32:
317-327,
1996[ISI][Medline].
55.
Takeyasu, K,
Tamkun MM,
Renaud KJ,
and
Fambrough DM.
Ouabain-sensitive (Na++K+)-ATPase activity expressed in mouse Ltk cell by transfection with DNA encoding
-subunit of an avian sodium pump.
J Biol Chem
263:
4347-4354,
1988
56.
Van Driel, IR,
and
Callaghan JM.
Proton and potassium transport by H+/K+-ATPases.
Clin Exp Pharmacol Physiol
22:
952-960,
1998.
57.
Verlander, JW,
Moudy RM,
Campbell WG,
Cain BD,
and
Wingo CS.
Immunohistochemical localization of H-K-ATPase 2c-subunit in rabbit kidney.
Am J Physiol Renal Physiol
281:
F357-F365,
2001
58.
Wang, Z,
Rabb H,
Craig T,
Burnham C,
Shull GE,
and
Soleimani M.
Ischemic-reperfusion injury in the kidney: overexpression of colonic H+-K+-ATPase and suppression of NHE-3.
Kidney Int
51:
1106-1115,
1997[ISI][Medline].
59.
Wilson, MJ,
and
Villee CA.
Preparation of prostatic plasma membranes. Distribution of (Na+,K+)-ATPase and Mg2+-ATPase in the rat ventral prostate.
Biochim Biophys Acta
394:
1-9,
1975[ISI][Medline].