1 Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521; and 2 Department of Animal Physiology, Lund University, Lund, Sweden
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ABSTRACT |
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Aquaporin-1 (AQP1) water channels are expressed widely in
epithelia and capillary endothelia involved in fluid transport. To test
whether AQP1 facilitates water movement from capillaries into the
peritoneal cavity, osmotically induced water transport rates were
compared in AQP1 knockout [(/
)], heterozygous
[(+/
)], and wild-type [(+/+)] mice. In (+/+) mice, RT-PCR
showed detectable transcripts for AQP1, AQP3, AQP4, AQP7, and AQP8.
Immunofluorescence showed AQP1 protein in capillary endothelia and
mesangium near the peritoneal surface and AQP4 in adherent muscle
plasmalemma. For measurement of water transport, 2 ml of saline
containing 300 mM sucrose (600 mosM) were infused rapidly into the
peritoneal cavity via a catheter. Serial fluid samples (50 µl) were
withdrawn over 60 min, with albumin as a volume marker. The albumin
dilution data showed significantly decreased initial volume influx in
AQP1 (
/
) mice: 101 ± 8, 107 ± 5, and 42 ± 4 (SE) µl/min in (+/+), (+/
), and (
/
) mice,
respectively [n = 6-10,
P < 0.001, (
/
) vs.
others]. Volume influx for AQP4 knockout mice was 100 ± 8 µl/min. In the absence of an osmotic gradient,
3H2O
uptake [half time = 2.3 and 2.2 min in (+/+) and
(
/
) mice, respectively],
[14C]urea uptake
[half time = 7.9 and 7.7 min in (+/+) and (
/
) mice,
respectively], and spontaneous isosmolar fluid absorption from
the peritoneal cavity [0.47 ± 0.05 and 0.46 ± 0.04 ml/h
in (+/+) and (
/
) mice, respectively] were not
affected by AQP1 deletion. Therefore, AQP1 provides a major route for
osmotically driven water transport across the peritoneal barrier in
peritoneal dialysis.
peritoneum; peritoneal dialysis; aquaporins; transgenic mice; water pores
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INTRODUCTION |
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THE PERITONEAL CAVITY is lined by a membranous barrier that provides a large surface for potential fluid movement between peritoneal capillaries and the peritoneal cavity. Although there is normally little fluid in the peritoneal cavity, marked ascites can occur in conditions associated with decreased serum oncotic pressure, increased portal venous pressure, or peritoneal cavity inflammation/infection. The large peritoneal surface is exploited in peritoneal dialysis, where water, electrolytes, urea, and uremia-causing toxins are extracted from blood by repeated infusion and removal of dialysate solutions into the peritoneal cavity. The kinetics of fluid and solute movement in peritoneal dialysis has been modeled extensively (18, 21). Some models postulate distinct classes of "pores" that transport water and different solutes to variable extents. An "ultrasmall," "water-only" pore has been postulated that is selective for water and responsible for the majority of osmotically induced water transport (17).
Recent studies suggest that aquaporin-type water channels might provide the molecular route for water movement through apparent ultrasmall pores in the peritoneal barrier. Aquaporin-1 (AQP1) has been localized to the peritoneum by RT-PCR and in situ hybridization (8), as well as by immunocytochemistry (3). In rat peritoneum, AQP1 has been localized to capillary endothelia and mesangium near the peritoneal luminal surface. AQP1 has also been detected in microvascular endothelial cells in peritoneal biopsies of humans with end-stage renal disease (16). Of the remaining aquaporins, transcript encoding AQP4 has been detected by RT-PCR in peritoneum (8), and AQP3 and AQP4 transcripts were detected in peritoneal dialysate (1); however, the expression and localization of AQP3 and AQP4 proteins have not been studied. Evidence was reported that AQP1 is functionally important in osmotic water movement across the peritoneal membrane in rats on the basis of effects of the mercurial inhibitor HgCl2 (3, 8). However, the data in these studies are difficult to interpret, because HgCl2 is highly toxic to peritoneal integrity and the differences in transport rates were small. In the study by Carlsson et al. (3), fixation of the peritoneum in vivo with glutaraldehyde was required before transport measurements to minimize solute leakage related to HgCl2 toxicity.
The purpose of this study was to determine the role of aquaporin-type water channels in osmotically (crystalloid) induced water transport into the peritoneal cavity. We confirmed the expression of AQP1, AQP3, and AQP4 transcript and carried out RT-PCR and immunocytochemistry to search for other aquaporins. The quantitative contributions of AQP1 and AQP4 to peritoneal osmotic water permeability were investigated using transgenic knockout mice lacking these water channels. The knockout mice were generated recently by targeted disruption of the AQP1 (13) and AQP4 (12) genes. The AQP4 mice had normal growth and appearance, with only a minor defect in urine-concentrating ability (12), despite a fourfold decrease in osmotic water permeability in the inner medullary collecting duct (5). The AQP1 mice had normal gross appearance when given access to food and water but became severely dehydrated when deprived of water because of inability to concentrate their urine (13, 19). The transport data reported here provide direct functional evidence for a role of AQP1 in in vivo osmotic water transport across the peritoneal barrier.
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METHODS |
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Transgenic mice. Transgenic knockout mice deficient in AQP1 and AQP4 protein were generated by targeted gene disruption, as described previously (12, 13). The knockout mice did not express detectable AQP1 or AQP4 protein in any organ. Measurements were done in tissues from litter-matched mice (6-8 wk of age) produced by intercrossing of CD1 heterozygotes. Genotype analysis of tail DNA was done by PCR at 5 days of age. The investigators were blinded to genotype information for all comparative permeability measurements.
Surgery. Mice were anesthetized during the experiment by methoxyflurane inhalation (Methofane, Mallinckrodt Veterinary, Mundelein, IL) in 100% O2 or by pentobarbital sodium (50 mg/kg body wt, Abbott Laboratories, North Chicago, IL). A 0.86-mm-ID catheter (PE-90, Clay Adams, Becton Dickinson, Parsippany, NJ) was inserted into the peritoneal cavity through an incision in the abdominal wall. The distal 0.6 cm of the catheter was perforated, and the end was enlarged for effective fluid sampling. The catheter was secured by a 3-0 silk purse-string suture to eliminate fluid leakage. Mice were kept supine throughout the study. The protocols for these studies were approved by the University of California San Francisco Animal Research Committee.
Permeability measurements. The peritoneal cavity was instilled via the catheter with 2.0 ml of solution over ~5 s by use of a 3-ml syringe. For most experiments the solution consisted of Ringer lactate containing 5% BSA (Sigma Chemical, St. Louis, MO) and 300 mM sucrose to give a final osmolality of ~600 mosM. Sucrose was omitted in control studies. In some experiments the instillate consisted of isosmolar Ringer lactate containing 3H2O (5 µCi/ml) and [14C]urea (1 µCi/ml; New England Nuclear, Bedford, MA). Fluid samples (50 µl) were obtained at specified times with a 1-ml syringe. Smaller presamples (10-25 µl) were withdrawn and discarded before each sample. The abdomen was intermittently gently agitated to facilitate fluid mixing. Samples were assayed for protein concentration by the biuret method. In some studies, 3H2O and [14C]urea radioactivities were assayed by scintillation counting. At the end of the experiment the abdomen was opened and the peritoneum was removed for planometric measurement of surface area.
To measure spontaneous isosmolar fluid transport, the peritoneal cavity of unanesthetized mice was infused with 2 ml of PBS containing 0.4 g/dl albumin by use of a 27-gauge needle. At a specific end point, 0.1 ml of the same solution containing 1 µCi of 125I-albumin (Merck Frosst) was infused as a dilutional volume marker. The mouse was killed after 3 min, and fluid samples were obtained from the left and right sides of the peritoneal cavity under direct visualization. Total peritoneal fluid volume was computed from the radioactivity in a fixed (generally 50 µl) fluid volume.RT-PCR. Freshly excised peritoneum from rat was carefully dissected from attached tissues. Rat was chosen because the larger tissue size permitted better dissection and because sequence information was available for the aquaporins. Total RNA was isolated by homogenization in TRIzol reagent (GIBCO BRL), and mRNA was extracted using the Oligotex mRNA midi kit (Qiagen). cDNA was reverse transcribed from mRNA with oligo(dT) (SuperScript II preamplification kit, BRL). PCR amplification was performed using the following primers: 5'-ATGTGGGAACTTCGGTCTGCCT-3' (sense) and 5'-CAATGTCTGAATTCCATTGAT-3' (antisense) for AQP0, 5'-ATGGCCAGCGAGTTAAAGAAGA-3' (sense) and 5'-TTTGGGCTTCATCTCCACCCTG-3' (antisense) for AQP1, 5'-ATGTGGGAACTCAGATCCATAG-3' (sense) and 5'-GGCCTTGCTGCCGCCAGGCAGG-3' (antisense) for AQP2, 5'-ATGAACCGTTGCGGCGAGATGC-3' (sense) and 5'-GATCTGCTCCTTGTGCTTCATG-3' (antisense) for AQP3, 5'-ATGGTGGCTTTCAAAGGCGTCTG-3' (sense) and 5'-CACACTCTCCATCTCCACGGCTC-3' (antisense) for AQP4, 5'-ATGAAAAAGGAGGTGTGCTCCCTTG-3' (sense) and 5'-GTGTGCCGTCAGCTCGATGGTC-3' (antisense) for AQP5, 5'-ATGGAGCCTGGGCTGTGTAACA-3' (sense) and 5'-TTACACGCTCACTTGTGTGTCC-3' (antisense) for AQP6, 5'-ATGGCCGGTTCTGTGCTGGAGA-3' (sense) and 5'-ACCCTGTGGTGGTATGCCGGCG-3' (antisense) for AQP7, and 5'-ATGTCTGGGGAGCAGACGCCGAT-3' (sense) and 5'-CCTCGACTTTAGAATCAGGCGG-3' (antisense) for AQP8. The PCR protocol was as follows: 94°C for 30 s, 55°C for 30 s, 72°C for 2 min, 30 cycles. The primers were derived from published aquaporin sequences with GenBank accession numbers X53052 (AQP0), L07268 (AQP1), D13906 (AQP2), D17695 (AQP3), U14007 (AQP4), U16254 (AQP5), AB005507 (AQP7), and AB005547 (AQP8). Templates for positive controls were cDNAs prepared from lens (AQP0), kidney (AQP1, AQP2, AQP3, and AQP6), brain (AQP4), lung (AQP5), and testes (AQP7 and AQP8). PCR products were electrophoresed on a 1% agarose gel.
Immunofluorescence. Peritoneal samples were removed, sliced, and fixed in 4% paraformaldehyde for 4 h. Samples were cryoprotected overnight with PBS containing 30% sucrose, embedded in OCT compound, and frozen in liquid N2. Cryostat sections (4-6 µm) were incubated for 10 min with PBS containing 1% BSA and then with AQP1-AQP5 antibodies for 1 h at 23°C in PBS containing 1% BSA, as described previously (6). Slides were rinsed with 2.7% NaCl and then with PBS and incubated for 30 min with Cy3-conjugated sheep anti-rabbit F(ab)2 fragment (1:200, Sigma Chemical).
Computations. Values are means ± SE with the number of mice indicated. For osmotically induced water flow, initial rates of volume flow for individual mice were determined from the slope of the albumin dilution curve at time 0, as determined from the derivative of a single exponential fitted to the first 10 min of the dilution curve. For 3H2O and [14C]urea uptake studies, half times (t1/2) were determined by single-exponential regression analysis. Significance was determined by Student's t-test.
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RESULTS |
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RT-PCR was done to determine which aquaporin transcripts are detectable in peritoneum. The peritoneal membrane was carefully dissected away from other tissues. The reverse-transcribed cDNA was used as template for amplifications with aquaporin-specific primers (amplifying coding sequences of AQP0-AQP8). Figure 1A shows that DNA fragments for AQP1, AQP3, AQP4, AQP7, and AQP8 were amplified from the peritoneal cDNA. DNA fragment identity was confirmed in each case by subcloning and sequence analysis. Positive controls are shown in the adjacent lanes with use of template cDNA from tissues known to express each aquaporin (see METHODS). The finding of AQP1, AQP3, and AQP4 transcripts in peritoneum is consistent with previous reports, as mentioned in the introduction.
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Immunofluorescence was carried out to determine the site(s) of
aquaporin protein expression by using available antibodies against
AQP1, AQP3, and AQP4. Figure 1, B and
C, shows AQP1 protein staining in
capillaries of the peritoneal barrier and mesangium near the surface,
consistent with previous findings (3). Staining of peritoneum from AQP1
knockout [(/
)] mice was negative (Fig. 1D). Staining was negative for AQP3
and AQP4, except for staining of adjacent diaphragmatic muscle by AQP4
antibody (Fig. 1E). AQP4 expression
in skeletal muscle has been demonstrated previously (7). Control
studies with the AQP3 antibody showed strong staining of kidney
collecting duct and tracheal epithelia (not shown), as reported
previously (6). Staining of peritoneum with antibodies against AQP2 and
AQP5 was also negative (not shown).
Functional measurements were done using knockout mice to determine
whether AQP1 facilitates osmotically induced water movement from
capillaries into the peritoneal cavity. The peritoneal cavity in
anesthetized mice was infused with a hyperosmolar solution (600 mosM)
containing 300 mM sucrose and a volume marker (5 g/dl albumin). The
time course of albumin dilution was measured in serial fluid samples
obtained by an indwelling peritoneal catheter. Figure
2A shows
the albumin dilution curves in one set of data on litter-matched
wild-type [(+/+)], AQP1 heterozygous [(+/)] and AQP1
(
/
) mice. The albumin concentrations in peritoneal fluid at the
earliest time point sampled (15 s) were slightly lower than that
infused (5 g/dl) because of residual peritoneal fluid present before
the infusion. There was a progressive decrease in albumin concentration
over time as water moved into the peritoneal cavity, with significantly
slowed dilution for the AQP1 (
/
) mice. Identical studies
performed with an isosmolar instillate (sucrose omitted) showed a small
increase in albumin concentration over time (Fig.
2A, control), indicating that the
albumin dilution results from osmotically driven water transport.
Similar measurements were done on AQP4 (
/
) mice to
determine whether the AQP4 in adjacent muscle increases peritoneal
water movement and because small amounts of AQP4 protein might be
present in peritoneum and not detected by immunostaining. AQP4 was
shown to have a substantially higher water permeability than the other
mammalian aquaporins (22), so relatively small amounts of AQP4 protein
might be functionally important. There were no significant differences
in the albumin dilution data between litter-matched (+/+) and AQP4
(
/
) mice (Fig. 2B).
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Initial volume flow rates (initial slope of albumin concentration vs.
time curve, see METHODS) are
summarized in Fig. 2C for each mouse
from several sets of paired studies. No significant differences in
initial volume flow were found for (+/+) vs. AQP1 (+/) and AQP4
(
/
) mice. Computed absolute volume influx rates (based on
2-ml initial volume) were 101 ± 8, 107 ± 5, 42 ± 4, and 100 ± 8 (SE) µl/min for (+/+)
(n = 10), AQP1 (+/
)
(n = 6) and (
/
)
(n = 6), and AQP4 (
/
)
(n = 4) mice, respectively. Initial influx was significantly decreased in the AQP1
(
/
) mice (P < 0.001).
This difference was not related to differences in peritoneal surface
area, which were measured at the end of each experiment: 21 ± 2 and
20 ± 1 cm2 smooth surface for
(+/+) and AQP1 (
/
) mice, respectively.
3H2O
uptake was measured in (+/+) and AQP1 (/
) mice in the
absence of an osmotic gradient. The peritoneal cavity was infused with
an isosmolar solution containing
3H2O,
and the time course of decreasing
3H radioactivity was measured in
serial peritoneal fluid samples. 3H radioactivity decreased by
diffusional water exchange between the peritoneal cavity and the
capillaries. The decrease was ~50% complete by 2-3 min; the
relative
3H2O
uptake at long times was ~0.18, representing the relative volumes of
infused peritoneal fluid vs. total body water. Quantitative determination of
t1/2
values by single-exponential regression yielded
t1/2
of 2.3 and 2.2 min for (+/+) and AQP1 (
/
) mice,
respectively (difference not significant). These results indicate that
the apparent rate of diffusional water exchange is not affected by AQP1
deletion. This result is consistent with the expectation that
diffusional water permeability in the complex peritoneal barrier is
unstirred layer limited and thus reflects the effective surface area
available for
3H2O
exchange. [14C]urea
uptake was measured to determine whether AQP1 deletion affects only the
water pathway. Figure
3B shows a
slow decrease in
[14C]urea
radioactivity over time, with 50% equilibration at ~8 min. Single-exponential regression indicated
t1/2
of 7.9 and 7.7 min for (+/+) and AQP1 (
/
) mice,
respectively (difference not significant). These results are consistent
with functional evidence that AQP1 is a water-selective transporting
protein (20, 23). The similar rates of
3H2O
and [14C]urea uptake
in (+/+) and AQP1 (
/
) mice indicate comparable effective
surface areas for these mice, supporting the conclusion that the
differences in osmotic water movement (Fig. 2,
A and C) are due to AQP1 deletion.
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These results indicate that AQP1 provides an important route for
osmotically driven water movement between the peritoneal cavity and
capillary compartment, as would be important for fluid extraction in
clinical peritoneal dialysis. To determine whether spontaneous
isosmolar fluid transport is affected by AQP1 deletion, fluid clearance
from the peritoneal cavity was measured as described in
METHODS. The peritoneal cavity of
unanesthetized mice was infused with 2 ml of an isosmolar solution. The
fluid volume remaining in the peritoneal cavity at specified times was
measured by the dilution of
125I-albumin, which was introduced
as a volume marker. Figure 4
(top) shows the time course of
peritoneal fluid clearance in (+/+) mice. Approximately 50% of the
infused fluid (1 ml) was cleared in 120 min under the conditions of
this experiment. To determine the effect of AQP1 deletion, fluid
samples were taken at 120 min in (+/+) and AQP1 (/
) mice.
Figure 4 (bottom) shows no
significant difference in the rate of spontaneous fluid clearance from
the peritoneal cavity.
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DISCUSSION |
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The purpose of this study was to test the hypothesis that AQP1 provides
a quantitatively important water-only pathway for osmotically induced
water movement across the peritoneal barrier. AQP1 deletion produced a
significant 2.4-fold reduction in osmotic water permeability. AQP1 was
expressed strongly in endothelial cells of peritoneal microvessels and
in mesangium near the peritoneal surface. Although transcripts encoding
several other aquaporin-type water channels were detected by RT-PCR, no
evidence was found for protein expression (for AQP3 and AQP4) in
relevant cell types on the peritoneal membrane and for the functional
importance of AQP4 in osmotic water permeability. The similar transport
rates of [14C]urea in
(+/+) and AQP1 (/
) mice supported the conclusion that AQP1 facilitates a water-only pathway across the peritoneal barrier. The similar transport rates of
3H2O
indicated that differences in osmotically induced water flow were not
due to differences in effective peritoneal surface area in (+/+) vs.
AQP1 (
/
) mice.
The detection of transcripts encoding AQP1, AQP3, and AQP4 in peritoneum by RT-PCR is consistent with previous results (1, 3, 8, 16). AQP1 protein was found only in endothelium and near-surface mesangium, whereas AQP4 protein was found only in the plasmalemma of diaphragmatic muscle. We believe that the AQP4 transcript detected by RT-PCR probably comes from contaminant muscle that cannot be dissected from the peritoneal membrane. AQP7 and AQP8 were also detected by RT-PCR. AQP7 is expressed strongly in testes and adipose tissue (9, 11); therefore, its presence, as detected by RT-PCR of peritoneal cDNA, may represent its expression in adherent peritoneal fat. AQP3 and AQP8 are expressed in the gastrointestinal system: AQP3 in colon (6) and AQP8 in adipocytes, pancreas, and colon (10, 14). However, AQP3 protein could not be detected by immunofluorescence or immunoblot analysis, so AQP3 protein levels are probably too low to provide a significant water pathway, particularly because of its relative low intrinsic water permeability (22). AQP7 and AQP8 antibodies were not available for immunostaining. The functional data here indicate that AQP1 is a major water channel of the peritoneal barrier but do not rule out the possibility that other aquaporins might have an important role as well, particularly considering the complex structure of the peritoneal barrier.
The reduced water permeability of the peritoneal barrier in AQP1
knockout mice compared with wild-type and heterozygous mice has
implications regarding the location of rate-limiting barriers to water
movement. Because a major site of AQP1 expression in the peritoneal
barrier is capillaries, the functional data suggest that the capillary
endothelium is an important barrier for osmotically driven water
transport. However, the generally accepted paradigm has been that water
permeability across microvascular endothelia is very high and does not
constitute a rate-limiting transport barrier. In renal vasa recta (15)
and lung microvessels (4), permeability is high, mercury sensitive, and
mediated by AQP1 water channels. The AQP1 (/
) mice are
unable to concentrate their urine in response to water deprivation (13)
and have a remarkably reduced water permeability between the air space
and capillary compartments in lung (2). Together these findings suggest
that capillaries can pose a significant barrier to osmotically driven
water transport.
The similar permeability of the peritoneal barrier in wild-type and
AQP1 heterozygous mice provides additional information about barriers
to water transport. On the basis of previous results in several organs
of AQP4 (+/) mice, AQP1 expression in (+/
) mice may be
~50% of that in (+/+) mice. (Quantitative immunoblotting of AQP1 in
dissected peritoneum could not be accomplished here.) For a single
rate-limiting barrier, a 50% reduction in AQP1 expression must give a
permeability equal to the average of those in (+/
) and
(
/
) mice. To account for the similar permeabililty in
(+/+) and (+/
) mice, it is necessary to postulate the existence
of a second barrier to water movement in series with the capillary barrier, as would be expected from the geometry of the peritoneal barrier. In AQP1 (
/
) mice, permeability is low, because
the capillary endothelial barrier is rate limiting. As the amount of
AQP1 increases, capillary water permeability increases until ultimately
a second barrier (peritoneal surface cells and/or interstitium) becomes rate limiting. Unfortunately, because of the complexity of the
peritoneal barrier and the AQP1-containing microvessels, a more
quantitative accounting of rate-limiting barriers is not possible.
Although osmotically induced water movement was significantly reduced
in AQP1 (/
) mice compared with (+/+) mice, spontaneous isosmolar fluid reabsorption was essentially unaffected. In kidney proximal tubule, transepithelial osmotic water permeability and active,
near-isosmolar fluid reabsorption are reduced in AQP1 (
/
)
mice (19). There are several possible explanations for the absence of
an effect of AQP1 deletion on isosmolar fluid reabsorption from the
peritoneal cavity: 1) rates of fluid
reabsorption across the peritoneal barrier are remarkably less than
those in kidney proximal tubule; 2)
the microvascular endothelium is not the site at which isosmolar fluid
transport occurs; and 3) other
mechanisms for fluid reabsorption from the peritoneal cavity exist such
as lymphatic flow. It would be potentially interesting to determine whether AQP1 deletion affects peritoneal fluid accumulation in models
of portal venous hypertension and peritoneal cavity tumor and infection.
In summary, AQP1 is a major water channel comprising the water-only pathway across the peritoneal barrier. The significant effect of AQP1 deletion on osmotically induced water transport indicates that AQP1 is an important determinant of the rate of water extraction in peritoneal dialysis. The absence of a significant effect of AQP1 deletion on slow isosmolar fluid absorption from the peritoneal cavity suggests that the AQP1 pathway has little or no role in clinically relevant mechanisms of peritoneal fluid accumulation and reabsorption.
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ACKNOWLEDGEMENTS |
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This work was supported by National Institutes of Health Grants DK-35124, HL-59198, HL-60288, HL-51854, and DK-43840, Gene Therapy Core Center Grant DK-47766, and National Cystic Fibrosis Foundation Research Development Program Grant R613.
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FOOTNOTES |
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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. §1734 solely to indicate this fact.
Address for reprint requests: A. S. Verkman, 1246 Health Sciences East Tower, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0521.
Received 12 June 1998; accepted in final form 31 August 1998.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Akiba, T.,
T. Ota,
K. Fushimi,
H. Tamura,
T. Hata,
S. Sasaki,
and
F. Marumo.
Water channel AQP1, 3, and 4 in human peritoneum and peritoneal dialysate.
Adv. Perit. Dial.
12:
3-6,
1997.
2.
Bai, C., M. A. Matthay, T. Ma, and A. S. Verkman. Role of aquaporin water channels in lung fluid transport:
phenotype analysis of aquaporin 1 and 4 knockout mice (Abstract).
Pediatr. Pulmonol. In
press.
3.
Carlsson, O.,
S. Nielsen,
E. R. Zakaria,
and
B. Rippe.
In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats.
Am. J. Physiol.
271 (Heart Circ. Physiol. 40):
H2254-H2262,
1996
4.
Carter, E. P.,
B. P. Ölveczky,
M. A. Matthay,
and
A. S. Verkman.
High microvascular endothelial water permeability in mouse lung measured by a pleural surface fluorescence method.
Biophys. J.
74:
2121-2128,
1998
5.
Chou, C. L.,
T. Ma,
B. Yang,
M. A. Knepper,
and
A. S. Verkman.
Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice.
Am. J. Physiol.
274 (Cell Physiol. 43):
C549-C554,
1998
6.
Frigeri, A.,
M. Gropper,
C. W. Turck,
and
A. S. Verkman.
Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes.
Proc. Natl. Acad. Sci. USA
92:
4328-4331,
1991[Abstract].
7.
Frigeri, A.,
M. Gropper,
F. Umenishi,
M. Kawashima,
D. Brown,
and
A. S. Verkman.
Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues.
J. Cell Sci.
108:
2993-3002,
1995
8.
Hayakawa, H.
Study of peritoneal water transporter expression in rats.
Jpn. J. Nephrol.
38:
535-544,
1996.
9.
Ishibashi, K.,
M. Kuwahara,
Y. Gu,
Y. Kegayama,
A. Tohsaka,
F. Marumo,
and
S. Sasaki.
Cloning and functional expression of a new water channel abundantly expressed in the testis also permeable to glycerol and urea.
J. Biol. Chem.
272:
20782-20786,
1997
10.
Koyama, Y.,
T. Yamamoto,
D. Kondo,
H. Funaki,
E. Yaoita,
K. Kawasaki,
N. Sato,
K. Hatakeyama,
and
I. Kihara.
Molecular cloning of a new aquaporin from rat pancreas and liver.
J. Biol. Chem.
272:
30329-30333,
1997
11.
Kuriyama, H.,
S. Kawamoto,
N. Ishida,
I. Ohno,
S. Mita,
Y. Matsuzawa,
K. Matsubara,
and
K. Okubo.
Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability.
Biochem. Biophys. Res. Commun.
241:
53-58,
1997[Medline].
12.
Ma, T.,
B. Yang,
A. Gillespie,
E. J. Carlson,
C. J. Epstein,
and
A. S. Verkman.
Generation and phenotype of a transgenic knock-out mouse lacking the mercurial-insensitive water channel aquaporin-4.
J. Clin. Invest.
100:
957-962,
1997
13.
Ma, T.,
B. Yang,
A. Gillespie,
E. J. Carlson,
C. J. Epstein,
and
A. S. Verkman.
Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels.
J. Biol. Chem.
273:
4296-4299,
1998
14.
Ma, T.,
B. Yang,
and
A. S. Verkman.
Cloning of a novel water- and urea-permeable aquaporin from mouse expressed strongly in colon, placenta, liver and heart.
Biochem. Biophys. Res. Commun.
240:
324-328,
1997[Medline].
15.
Pallone, T. L.,
B. K. Kishore,
S. Nielsen,
P. Agre,
and
M. A. Knepper.
Evidence that aquaporin-1 mediates NaCl-induced water flux across descending vasa recta.
Am. J. Physiol.
272 (Renal Fluid Electrolyte Physiol. 41):
F587-F596,
1997
16.
Pennekeet, M. M.,
J. B. Mulder,
J. J. Weening,
D. G. Struljk,
M. M. Zweers,
and
R. T. Krediet.
Demonstration of aquaporin-CHIP in peritoneal tissues of uremic and CAPD patients.
Perit. Dial. Int.
16:
S54-S57,
1996[Medline].
17.
Rippe, B.
A three-pore model of peritoneal transport.
Perit. Dial. Int.
13:
S35-S38,
1993[Medline].
18.
Rippe, B.,
and
G. Stelin.
Simulations of peritoneal solute transport during CAPD. Application of two-pore formalism.
Kidney Int.
35:
1234-1244,
1989[Medline].
19.
Schnermann, J.,
J. Chou,
T. Ma,
T. Traynor,
M. A. Knepper,
and
A. S. Verkman.
Defective proximal tubule reabsorption in transgenic aquaporin-1 null mice.
Proc. Natl. Acad. Sci. USA
95:
9660-9664,
1998
20.
Van Hoek, A. N.,
and
A. S. Verkman.
Functional reconstitution of the isolated erythrocyte water channel CHIP28.
J. Biol. Chem.
267:
18267-18269,
1992
21.
Vonesh, E. F.,
J. Burkart,
D. McMurray,
and
P. F. Williams.
Peritoneal dialysis kinetic modeling: validation in a multicenter clinical study.
Perit. Dial. Int.
16:
471-481,
1996[Medline].
22.
Yang, B.,
and
A. S. Verkman.
Water and glycerol permeability of aquaporins 1-5 and MIP determined quantitatively by expression of epitope-tagged constructs in Xenopus oocytes.
J. Biol. Chem.
272:
16140-16146,
1997
23.
Zeidel, M. L.,
S. V. Ambudkar,
B. L. Smith,
and
P. Agre.
Reconstitution of functional water channels in liposomes containing purified red cell CHIP28 protein.
Biochemistry
31:
7436-7440,
1992[Medline].