1 Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, S-171 76 Stockholm, Sweden; 2 Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus, Denmark; 3 Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021-6399; and 4 Laboratory of Physiological Genetics, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Lavrentyeva, 630090 Novosibirsk, Russia
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ABSTRACT |
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Prostaglandin E2 (PGE2)
antagonizes the action of arginine vasopressin (AVP) on collecting duct
water permeability. To investigate the mechanism of this
antagonism, rat renal inner medulla (IM) was incubated with the two
hormones, and the phosphorylation and subcellular distribution of the
water channel, aquaporin-2 (AQP2) were studied. Using a phosphorylation
state-specific AQP2 antibody, we demonstrated that AVP stimulates AQP2
phosphorylation at the Ser256 protein kinase A consensus
site in a time- and dose-dependent manner. In parallel studies using a
differential centrifugation technique, we demonstrated that AVP induced
translocation of AQP2 from an intracellular vesicle-enriched fraction
to a plasma membrane-enriched fraction. PGE2
(107 M) added after AVP
(10
8 M) did not decrease AQP2
phosphorylation but reversed AVP-induced translocation of AQP2 to the
plasma membrane. Preincubation of IM with PGE2 did not
prevent the effects of AVP on AQP2 phosphorylation and trafficking.
PGE2 alone did not influence AQP2 phosphorylation and
subcellular distribution. Our data indicate that 1) recruitment of AQP2 to the plasma membrane and its retrieval to a pool of intracellular vesicles may be regulated independently, 2)
PGE2 may counteract AVP action by activation of AQP2
retrieval, 3) dephosphorylation of AQP2 is not a prerequisite
for its internalization.
inner medulla; vesicular traffic; hormonal regulation; exocytosis; endocytosis
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INTRODUCTION |
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CONDITIONS OF INAPPROPRIATE water retention are not always associated with high levels of the antidiuretic hormone arginine vasopressin (AVP) (31, 35, 50). This indicates that water excretion may be regulated by other first messengers, acting either in concert or in opposition to AVP. The identification of such factors and their mechanism of action would allow for a more specific therapy in often life-threatening conditions of water retention. Prostaglandin E2 (PGE2), which is the major cyclooxygenase product of arachidonate metabolism in collecting duct in humans, rabbits, and rats (5, 14, 51), may be one such factor. Both endogenous and exogenous prostaglandins can reverse the effect of AVP on water permeability in rat and rabbit collecting duct (27, 43, 55). However, the mechanism(s) involved in the interaction between AVP and prostaglandins has not been well characterized.
In the collecting duct the actions of AVP are mediated through the activation of the water channel aquaporin-2 (AQP2) (20, 21, 45, 46). In the absence of AVP, a large fraction of AQP2 is localized to vesicles in the cytoplasm of collecting duct principal cells (46). AVP stimulates water permeability by inducing the translocation of AQP2 to the apical membrane of the cell (41, 45, 54, 59), a process that appears to result from activation of protein kinase A (PKA) and phosphorylation of Ser256 in AQP2 (19, 33, 36, 48).
In the present study, we have examined the effect of PGE2 on the actions of AVP in rat renal medulla. By use of a phosphorylation state-specific AQP2 antibody, it was demonstrated that PGE2 does not reduce AVP-induced phosphorylation of AQP2 at Ser256. However, as demonstrated by subcellular fractionation, PGE2 reversed the AVP-induced increase of the plasma membrane fraction of AQP2. Preincubation with PGE2 did not prevent the effect of AVP on AQP2 phosphorylation and translocation to the plasma membrane. The results indicate that PGE2 acts by retrieving AQP2 that has been recruited to the plasma membrane by AVP but that dephosphorylation of AQP2 is not required for this process.
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METHODS |
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Processing of rat inner medullary tissue. The studies were
performed on male Sprague-Dawley rats (B&K Universal, Sollentura, Sweden) that were fed a standard rat chow and had free
access to normal drinking water. Rats were anesthetized with
thiobutabarbital (8 mg/100 g body wt), the kidneys were rapidly
removed, and the inner medulla was excised and processed immediately.
All studies were started between 8 and 9 AM. In some protocols, rats
were treated with indomethacin (1 mg/100 g body wt; Confortid, Dumex, Copenhagen, Denmark) given 16 and 1 h before the
experiment to suppress the endogenous production of prostaglandins
(17). Indomethacin (105 M) was added to
all solutions during processing of tissue from indomethacin-treated rats.
After excision, the inner medullary tissue was kept at 30°C, since cold treatment can change the distribution of AQP2 in collecting duct cells and inhibit AVP-stimulated translocation of AQP2 to the apical membrane (6). The inner medulla from each rat was divided into four or six equal pieces. It has been shown that the level of AQP2 gradually changes from the outer medulla to the tip of the inner medulla (34). Therefore, dissection of the tissue was made in a radial direction from the medullary tip toward the edge that contacted the inner strip of the outer medulla. In every experiment, one portion of the dissected tissue was used as a control; the other portions of dissected tissue from the same rat were used for the various drug treatments. In tissue fractionation experiments, the tissues from two to three animals were pooled, with one piece from each animal combined in every sample.
The excised tissue was incubated at 30°C in saline solution (in mM: 137 NaCl, 5 KCl, 0.8 MgSO4, 0.33 Na2HPO4, 0.44 KH2PO4, and 1 MgCl2) bubbled with 95% O2-5% CO2 (vol/vol). After ~30 min, the tissue was transferred to a new portion of the solution; hormones, drugs, or vehicle were added; and the tissue was incubated for the indicated periods of time. After incubation, the tissue was homogenized in buffer A [in mM: 300 sucrose, 25 imidazole, 1 EDTA, pH 7.2; containing the protease inhibitors 5 µg/ml leupeptin and 1 mM phenylmethylsulfonyl fluoride (PMSF); and protein phosphatase inhibitors 25 mM sodium fluoride, 1 mM sodium orthovanadate, and 0.1 µM okadaic acid]. The homogenate was suspended in Laemmli sample buffer, heated at 100°C for 5 min, analyzed for protein concentration using the Lowry method, and subjected to SDS-PAGE (10 µg protein/lane).
For tissue fractionation, the medulla was homogenized in buffer B (in mM: 300 sucrose, 25 imidazole, 1 EDTA, pH 7.2; containing protease inhibitors 20 µg/ml leupeptin, 20 µg/ml antipain, 5 µg/ml pepstatin A, 5 µg/ml chymostatin, and 1 mM PMSF; peptidase inhibitor 25 mM benzamidine; and protein phosphatase inhibitors 25 mM sodium fluoride, 1 mM sodium orthovanadate, and 0.1 µM okadaic acid). Fractionation was performed as described (41) using three consecutive centrifugation steps. 1) The homogenate was centrifuged at 4,000 g for 10 min, and the pellet containing nuclei and cell debris was discarded. 2) The supernatant was centrifuged at 17,000 g for 30 min. The pellet was resuspended in buffer B and considered as the plasma membrane-enriched fraction (M). 3) The supernatant from step 2 was centrifuged at 200,000 g for 1 h. The pellet was resuspended in buffer B and considered as the intracellular vesicle-enriched fraction (V). Both M and V fractions were suspended in Laemmli sample buffer, heated at 100°C for 5 min, analyzed for protein concentration using the Lowry method, and subjected to SDS-PAGE (10 µg protein/lane).
Western blotting. After electrophoresis, the proteins were transferred to Hybond-P polyvinylidene difluoride (PVDF) membrane (Amersham Sweden, Uppsala, Sweden) by electroelution. The membrane was blocked in 5% nonfat dry milk (wt/vol) in PBST (80 mM Na2HPO4, 20 mM NaH2PO4, and 100 mM NaCl, pH 7.5; Tween-20 0.1%), and AQP2 phosphorylated at Ser256 was detected with a double affinity-purified phosphorylation state-specific rabbit antibody, AN83-2 (48). The antibody was raised against a synthetic peptide corresponding to amino acids 253-262 of rat AQP2. The peptide was chemically phosphorylated at Ser256, and amino acids 259 and 260 were swapped to reduce antigenicity outside the phosphorylation site. The peptide and antibody were prepared by the Rockefeller University Protein/DNA Technology Center, New York, NY, and AnaSpec, San Jose, CA. The total amount of AQP2 was evaluated using LL127 rabbit antiserum (described in Ref. 46) raised against a synthetic peptide corresponding to amino acids 250-271 of rat AQP2. Visualization of the proteins was performed using goat anti-rabbit horseradish peroxidase-conjugated IgG and ECL Plus Western blotting analysis system (Amersham Sweden).
After immunodetection, the PVDF membranes were stained for 5 min with amido black at room temperature and with constant shaking (amido black-10B, 0.1% wt/vol; methanol, 10% vol/vol; and acetic acid, 2% vol/vol), then three to four times for 5 min in destaining solution (methanol, 45% vol/vol; acetic acid, 7% vol/vol).
In some experiments, the PVDF membranes were consecutively probed with both AN83-2 and LL127 antibodies. After the first immunodetection, washing was performed according the manufacturer's recommendations. The PVDF membrane was incubated in stripping buffer (62.5 mM Tris · HCl, pH 6.7, 2% SDS, and 100 mM 2-mercaptoethanol) for 30 min at 50°C, then in PBST twice for 10 min at room temperature. After washing, the procedure of immunodetection was repeated using the second antibodies.
Data analysis and statistics. The X-ray films and stained PVDF membranes were scanned using a HP ScanJet 5100C and HP PrecisionScan software (Hewlett-Packard Sverige, Kista, Sweden). The images obtained were analyzed using NIH Image 1.57 software. In all cases, the antibody signal was normalized for total protein calculated from the amido black staining in each lane. The values obtained for each experimental sample were expressed as a percentage of that obtained for the corresponding control sample from the same animal. Data are presented as means ± SE. Statistical analyses were made using Student's t-test. A difference of P < 0.05 was considered statistically significant.
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RESULTS |
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AVP-dependent AQP2 phosphorylation in rat renal inner medulla.
To investigate PKA-dependent AQP2 phosphorylation in rat renal medulla and to establish the conditions necessary for the studies described below, we used the antibody that specifically recognizes AQP2
phosphorylated at Ser256. Both the glycosylated and
nonglycosylated forms of AQP2 were partially phosphorylated at
Ser256 in control tissue (Fig.
1A), suggesting that there is a
constitutive activation of PKA in rat inner medulla. The basal AQP2
phosphorylation did not change significantly during 60 min of
incubation (Fig. 1C, ). Incubation of the tissue with AVP
(10
8 M) increased AQP2 phosphorylation
at Ser256 significantly after 1 min of incubation (Fig.
1C,
). A maximal level was reached after 7 min and this was
sustained for 30 min. After 60 min of incubation with AVP, the level of
Ser256 phosphorylation was significantly lower than
after 30 min and did not differ from that observed in control samples
incubated without AVP.
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AVP stimulated AQP2 phosphorylation in a dose-dependent manner (Fig. 1,
D and F). The level of AQP2 phosphorylation was
significantly increased at 1010 M AVP.
To check that the amount of AQP2 was the same in all samples, the
filters were reprobed with an antibody that recognizes both phosphorylated and nonphosphorylated forms of AQP2 (9a). The total AQP2
abundance was the same at each time point and AVP concentration (Fig.
1, B and E).
Effect of PGE2 on AQP2 phosphorylation
in inner medullary tissue. In this series of experiments, rats were
pretreated with indomethacin to suppress endogenous PG production. One
part of excised inner medulla was incubated with vehicle for 30 min and another part with AVP (108 M) for 30 min
(Fig. 2A). Using this protocol AVP
increased AQP2 phosphorylation more than twofold (Fig. 2, B and
C). It has previously been shown that addition of
10
7 M PGE2 to perfused rat
and rabbit collecting ducts incubated with 1-2.3 × 10
11 M AVP significantly reduced the
AVP-stimulated water permeability (27, 43). Therefore, a third portion
of the medulla was also incubated with AVP for 30 min, but after 15 min, PGE2 (10
7 M) was added.
A fourth piece of the tissue from the same animal was incubated with
vehicle for 15 min and then with PGE2
(10
7 M) for 15 min. PGE2 did
not have any effect on AQP2 Ser256 phosphorylation (Fig.
2, B and C). The level of AQP2 phosphorylation in
samples preincubated with AVP for 15 min and then incubated with AVP
and PGE2 for 15 min was significantly higher than in vehicle-treated tissue and did not differ from that in medulla incubated with AVP alone for 30 min. PGE2 alone did not
influence the level of AQP2 Ser256 phosphorylation in rat
inner medullary tissue.
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Effect of AVP and PGE2 on AQP2 subcellular distribution in inner medulla. After incubation with hormones, inner medulla samples were fractionated using consecutive centrifugation steps to obtain a plasma membrane-enriched fraction (M) and an intracellular vesicle-enriched fraction (V). The adequacy of this method is well established (41, 47, 57).
The levels of AQP2 in the M and V fractions were measured using the
antibody that recognized both the phosphorylated and nonphosphorylated forms of the protein. In samples from indomethacin-treated, normally hydrated rats, ~60% of total AQP2 were present in the M fraction (Fig. 3A). Incubation with AVP
(108 M) for 30 min caused a notable
translocation of AQP2 from the V to the M fraction (Fig. 3, A
and C). AVP-induced increase in M/V ratio was significant after
5 min of incubation of rat inner medulla with AVP. It was sustained for
~30 min but had returned to control values after 60 min (not shown).
The effect of AVP on AQP2 translocation was reversed if
PGE2 (10
7 M) was added to
the incubation medium during the last 15 min of incubation with AVP.
The M/V ratio was significantly lower in AVP+PGE2-treated
tissue compared with AVP-treated tissue and did not
differ from that of control tissue. The application of PGE2
(10
7 M) alone for 15 min did not change
AQP2 distribution compared with control. The fraction of AQP2 that was
phosphorylated was increased to the same extent in M and V fractions of
tissue treated with AVP (Table 1). It was
not decreased in any fraction after PGE2 addition to
AVP-treated papillae. PGE2 alone did not influence the
state of AQP2 phosphorylation.
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In the next series of experiments, renal inner medullary tissue from
indomethacin-treated rats was preincubated with PGE2 (107 M) for 25 min, and then AVP
(10
8 M) was added to the incubation
medium for 5 min (Fig. 4A).
Preincubation with PGE2 did not prevent the effect of AVP
on phosphorylation or distribution of AQP2. Both AQP2 phosphorylation
and the AQP2 M/V ratio were significantly higher in
PGE2+AVP-treated tissue compared with control tissue and
did not differ from tissue treated with AVP alone for 5 min (Fig. 4,
B and C).
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DISCUSSION |
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It is well documented that AQP2, inserted in vesicles in the cytoplasm, will be translocated to the plasma membrane following activation of V2 receptors by AVP (41, 45, 54, 59). In addition, studies using cells transfected with AQP2 suggest that PKA activation and phosphorylation of AQP2 are necessary for the targeting of the protein to the membrane (11, 19, 33). The results from the present study are consistent with this hypothesis. It should be noted, however, that additional proteins, known to be important for vesicular trafficking, have been shown to be phosphorylated by PKA (14, 26). AVP action may also involve activation of protein kinase C (PKC) (2, 54), which phosphorylates other proteins specifically linked to regulated exocytosis (16, 18, 39). Moreover, AVP increases intracellular calcium concentration in collecting ducts (8, 9, 13), raising the possibility that Ca2+/calmodulin-dependent protein kinases (CaMK) could be activated. Notably, CaMKII phosphorylates a broad spectrum of components of the vesicle trafficking system (22, 28, 44, 52, 53). Thus it is not unlikely that the targeting of the AQP2-containing vesicles to the plasma membrane is associated with a series of phosphorylation events that regulate multiple protein-protein interactions involved in the vesicle trafficking.
In the present study, the AVP concentrations necessary to stimulate
phosphorylation of AQP2 were similar to those observed in
water-deprived rats (32). However, both the time course and the
effective AVP level might be underestimated in our experiments, since
AVP had to penetrate several cellular layers to reach the entire volume
of tissue. The AVP-induced phosphorylation of AQP2 was rapid and lasted
for ~30 min, but between 30 and 60 min significant dephosphorylation
occurred. This effect may be attributed to a gradual degradation of AVP
in incubation medium and to the action of protein phosphatases, which
are abundantly expressed in rat inner medulla (7, 38, 58). The
progressive loss of AQP2 32P labeling following exogenous
PKA-stimulated AQP2 phosphorylation has been previously observed in rat
papillary water channel-containing vesicle preparations (37). The
presence of protein phosphatase 2B (PP2B or calcineurin), as well as
type II regulatory subunit of PKA and -isoform of protein kinase C
(PKC-
), has been recently demonstrated in AQP2-bearing
vesicles (29). The colocalization of protein kinases, protein
phosphatases, and AQP2 could provide operative and precise regulation
of the state of phosphorylation of this water channel.
In our experiments, AVP-induced redistribution of AQP2 was significant starting from 5 min up to 30 min of incubation of the tissue with the hormone. By 60 min of the incubation, AQP2 distribution returned to that in control tissue, probably due to AVP stimulation exhaustion. In a parallel study performed in Wistar and Brattleboro rats (9a) we have shown that in vivo the AQP2 redistribution effect of more degradation-resistant vasopressin analog 1-desamino-8-D-arginine vasopressin (dDAVP) lasted up to 2 h. By that time there was no increase in total amount of phosphorylated AQP2, suggesting a hypothesis that sustained phosphorylation may not be required for AQP2 to stay in the apical membrane.
In these studies, PGE2 alone did not have any effect on AQP2 phosphorylation or on its subcellular distribution. These results agree with other studies in rat collecting duct where PGE2 has no effect on cAMP production (40) or on water permeability (41), in contrast to the situation in rabbits (3, 25, 43). However, in these studies, PGE2 stimulated the retrieval of AQP2 from the plasma membrane in AVP-stimulated tissue. Theoretically, PGE2 might have interrupted an AVP-induced continuous supply of AQP2 to the plasma membrane or stimulate endocytosis of AQP2. The finding that preincubation with PGE2 did not prevent AVP-stimulated recruitment of AQP2 to the plasma membrane tends to support the latter possibility.
The cellular mechanism by which PGE2 may regulate retrieval of AQP2 from the membrane remains to be elucidated. In collecting duct, PGE2 may interact with several types of PG receptors, including EP1, EP2, EP3, and EP4 (23, 24, 27, 49). These receptors can activate a variety of signaling pathways including activation (EP2 and EP4) and inhibition (EP3) of adenylyl cyclase and activation of phospholipase C (EP1). Both EP1 and EP3 prostaglandin receptors might participate in the PGE2-induced endocytosis of AQP2 observed in our studies. Our results indicate that dephosphorylation of AQP2 is not a prerequisite for its retrieval from the plasma membrane. It is not excluded, however, that an EP3-mediated decrease in intracellular cAMP level may lead to PGE2-induced redistribution of AQP2 via dephosphorylation of other proteins involved in vesicle trafficking. On the other hand, it is known that pretreatment with pertussis toxin does not prevent the ability of PGE2 to reverse the effects of AVP (1, 49). There is also clear evidence for role of PKC (4, 23, 41, 47) and Ca2+ (1, 26) in mediating the PGE2 action.
We suggest that the distribution of AQP2 in rat inner medulla is regulated by a balance between AVP and PGE2. Decrease in PGE2 production by cyclooxygenase inhibitors would lead to a reduction of AQP2 endocytosis and therefore to increased abundance of AQP2 in the plasma membrane. This hypothesis is in a good agreement with observations that 2 days of indomethacin or diclofenac treatment induces a striking shift of AQP2 from intracellular vesicle-enriched fraction to the plasma membrane-enriched fraction of rat inner medulla (14).
The finding that PGE2 reverses the AVP-induced redistribution of AQP2 to the plasma membrane, may have important pathophysiological implications. Indomethacin therapy to suppress endogenous PG production is widely used to close patent ductus arteriosus in infants, and water retention is not an uncommon complication of this therapy (10, 30). Notably, PGE2 counteracts the effect of AVP on water permeability in the collecting duct in several species, including rabbit and rat (27, 43, 55), and clearance studies suggest that such a bidirectional regulation of water permeability by AVP and PGE2 also exists in man (12).
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ACKNOWLEDGEMENTS |
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This work was supported by grants from the Swedish Medical Research Council (03644), the Swedish Heart-Lung Foundation, Märta and Gunnar V. Philipson Foundation, the University of Aarhus, and the EU Commission (TMR and Biotech programs).
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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 and other correspondence: A. Aperia, Q2:09 Astrid Lindgren Children's Hospital, S-171 76 Stockholm, Sweden (E-mail: aniap{at}child.ks.se).
Received 12 February 1999; accepted in final form 12 October 1999.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Aarab, L.,
M. Montegut,
S. Siaume-Perez,
M. Imbert-Teboul,
and
D. Chabardes.
PGE2-induced inhibition of AVP-dependent cAMP accumulation in the OMCD of the rat kidney is cumulative with respect to the effects of alpha 2-adrenergic and alpha 1-adenosine agonists, insensitive to pertussis toxin and dependent on extracellular calcium.
Pflügers Arch.
423:
397-405,
1993[ISI][Medline].
2.
Ali, N.,
S. Kantachuvesiri,
J. I. Smallwood,
L. J. Macala,
C. Isales,
J. Ji,
R. Reilly,
and
J. P. Hayslett.
Vasopressin-induced activation of protein kinase C in renal epithelial cells.
Biochim. Biophys. Acta
1402:
188-196,
1998[ISI][Medline].
3.
Ando, Y.,
and
Y. Asano.
Luminal prostaglandin E2 modulates sodium and water transport in rabbit cortical collecting ducts.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
268:
F1093-F1101,
1995
4.
Aristimuño, P. C.,
and
D. W. Good.
PKC isoforms in rat medullary thick ascending limb: selective activation of the -isoform by PGE2.
Am. J. Physiol. Renal Physiol.
272:
F624-F631,
1997
5.
Bonvalet, J. P.,
P. Pradelles,
and
N. Farman.
Segmental synthesis and actions of prostaglandins along the nephron.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
253:
F377-F387,
1987
6.
Breton, S.,
and
D. Brown.
Cold-induced microtubule disruption and relocalization of membrane proteins in kidney epithelial cells.
J. Am. Soc. Nephrol.
9:
155-166,
1998[Abstract].
7.
Buttini, M.,
S. Limonta,
M. Luyten,
and
H. Boddeke.
Distribution of calcineurin A isoenzyme mRNAs in rat thymus and kidney.
Histochem. J.
27:
291-299,
1995[ISI][Medline].
8.
Champigneulle, A.,
E. Siga,
G. Vassent,
and
M. Imbert-Teboul.
V2-like vasopressin receptor mobilizes intracellular Ca2+ in rat medullary collecting tubules.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
265:
F35-F45,
1993
9.
Chou, C.-L.,
S. I. Rapko,
and
M. A. Knepper.
Phosphoinositide signaling in rat inner medullary collecting duct.
Am. J. Physiol. Renal Physiol.
274:
F564-F572,
1998
9a.
Christensen, B. M.,
M. Zelenina,
A. Aperia,
and
S. Nielsen.
Localization and regulation of PKA-phosphorylated AQP2 in response to V2-receptor agonist/antagonist treatment.
Am. J. Physiol. Renal Physiol.
278:
F29-F42,
2000
10.
Cifuentes, R. F.,
P. M. Olley,
J. W. Balfe,
I. C. Radde,
and
S. J. Soldin.
Indomethacin and renal function in premature infants with persistent patent ductus arteriosus.
J. Pediatr.
95:
583-587,
1979[ISI][Medline].
11.
Deen, P. M.,
J. P. Rijss,
S. M. Mulders,
R. J. Errington,
J. van Baal,
and
C. H. van Os.
Aquaporin-2 transfection of Madin-Darby canine kidney cells reconstitutes vasopressin-regulated transcellular osmotic water transport.
J. Am. Soc. Nephrol.
8:
1493-501,
1997[Abstract].
12.
Dixey, J. J.,
T. D. Williams,
S. L. Lightman,
A. F. Lant,
and
D. A. Brewerton.
The effect of indomethacin on the renal response to arginine vasopressin in man.
Clin. Sci.
70:
409-16,
1986[ISI][Medline].
13.
Ecelbarger, C. A.,
C. L. Chou,
S. J. Lolait,
M. A. Knepper,
and
S. R. DiGiovanni.
Evidence for dual signaling pathways for V2 vasopressin receptor in rat inner medullary collecting duct.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
270:
F623-F633,
1996
14.
Ecelbarger, C. A.,
P. Fernández-Llama,
A. J. Lee,
S. Nielsen,
J. A. Ware,
S. Shen,
L. R. Pohl,
and
M. A. Knepper.
Enhancement of urinary concentrating ability by cyclooxygenase inhibitors is associated with increased expression of Na-K-2Cl cotransporter and increased trafficking of aquaporin-2 water channel (Abstract).
J. Am. Soc. Nephrol.
8:
413,
1997.
15.
Fernandez-Tome, M. C.,
C. D'Antuono,
V. L. Kahane,
E. H. Speziale,
and
N. B. Sterin-Speziale.
Compartmental study of rat renal prostaglandin synthesis during development.
Biol. Neonate
70:
235-245,
1996[ISI][Medline].
16.
Foster, L. J.,
B. Yeung,
M. Mohtashami,
K. Ross,
W. S. Trimble,
and
A. Klip.
Binary interactions of the SNARE proteins syntaxin-4, SNAP23, and VAMP-2 and their regulation by phosphorylation.
Biochemistry
37:
11089-11096,
1998[ISI][Medline].
17.
Francisco, L. L.,
J. L. Osborn,
and
G. F. DiBona.
Prostaglandins in renin release during sodium deprivation.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
243:
F537-F542,
1982
18.
Fujita, Y.,
T. Sasaki,
K. Fukui,
H. Kotani,
T. Kimura,
Y. Hata,
T. C. Sudhof,
R. H. Scheller,
and
Y. Takai.
Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C. Its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin.
J. Biol. Chem.
271:
7265-7268,
1996
19.
Fushimi, K.,
S. Sasaki,
and
F. Marumo.
Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel.
J. Biol. Chem.
272:
14800-14804,
1997
20.
Fushimi, K.,
S. Sasaki,
T. Yamamoto,
M. Hayashi,
T. Furukawa,
S. Uchida,
M. Kuwahara,
K. Ishibashi,
M. Kawasaki,
and
I. Kihara.
Functional characterization and cell immunolocalization of AQP-CD water channel in kidney collecting duct.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
267:
F573-F582,
1994
21.
Fushimi, K.,
S. Uchida,
Y. Hara,
Y. Hirata,
F. Marumo,
and
S. Sasaki.
Cloning and expression of apical membrane water channel of rat kidney collecting tubule.
Nature
361:
549-552,
1993[ISI][Medline].
22.
Greengard, P.,
F. Valtorta,
A. J. Czernik,
and
F. Benfenati.
Synaptic vesicle phosphoproteins and regulation of synaptic function.
Science
259:
780-785,
1993[ISI][Medline].
23.
Hao, C. M.,
L. J. Ma,
Y. G. Guan,
L. S. Davis,
R. F. Redha,
R. M. Breyer,
and
M. D. Breyer.
Intra-renal expression of the prostaglandin EP4 receptor and its regulation by dietary Na+ restriction (Abstract).
J. Am. Soc. Nephrol.
9:
412,
1998.
24.
Hébert, R. L.,
R. M. Breyer,
H. R. Jacobson,
and
M. D. Breyer.
Functional and molecular aspects of prostaglandin E receptors in the cortical collecting duct.
Can. J. Physiol. Pharmacol.
73:
172-179,
1995[ISI][Medline].
25.
Hébert, R. L.,
H. R. Jacobson,
and
M. D. Breyer.
PGE2 inhibits AVP-induced water flow in cortical collecting ducts by protein kinase C activation.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
259:
F318-F325,
1990
26.
Hébert, R. L.,
H. R. Jacobson,
and
M. D. Breyer.
Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium.
J. Clin. Invest.
87:
1992-1998,
1991[ISI][Medline].
27.
Hébert, R. L.,
H. R. Jacobson,
D. Fredin,
and
M. D. Breyer.
Evidence that separate PGE2 receptors modulate water and sodium transport in rabbit cortical collecting duct.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
265:
F643-F650,
1993
28.
Hirling, H.,
and
R. H. Scheller.
Phosphorylation of synaptic vesicle proteins: Modulation of the SNAP interaction with the core complex.
Proc. Natl. Acad. Sci. USA
93:
11945-11949,
1996
29.
Jo, I.,
M. Baum,
J. D. Scott,
V. M. Coghlan,
and
H. W. Harris.
Aquaporin 2-containing apical membrane endosomes (AQP-2 endosomes) possess a multiprotein signalling complex similar to that present in brain neurons (Abstract).
J. Am. Soc. Nephrology
8:
19,
1997.
30.
John, E. G.,
U. Vasan,
A. R. Hastreiter,
R. Bhat,
and
M. A. Evans.
Intravenous indomethacin and changes of renal function in premature infants with patent ductus arteriosus.
Pediatr. Pharmacol. (New York)
4:
11-19,
1984[Medline].
31.
Johnson, A. G.
NSAIDs and blood pressure. Clinical importance for older patients.
Drugs Aging
12:
17-27,
1998[ISI][Medline].
32.
Kadekaro, M.,
J. Y. Summy-Long,
S. Freeman,
J. S. Harris,
M. L. Terrell,
and
H. M. Eisenberg.
Cerebral metabolic responses and vasopressin and oxytocin secretions during progressive water deprivation in rats.
Am. J. Physiol. Regulatory Integrative Comp. Physiol.
262:
R310-R317,
1992
33.
Katsura, T.,
C. E. Gustafson,
D. A. Ausiello,
and
D. Brown.
Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells.
Am. J. Physiol. Renal Physiol.
272:
F816-F822,
1997[ISI].
34.
Kishore, B. K.,
J. M. Terris,
and
M. A. Knepper.
Quantitation of aquaporin-2 abundance in microdissected collecting ducts: axial distribution and control by AVP.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
271:
F62-F70,
1996
35.
Kohan, D. E.
Endothelins in the normal and diseased kidney.
Am. J. Kidney Dis.
29:
2-26,
1997[ISI][Medline].
36.
Kuwahara, M.,
K. Fushimi,
Y. Terada,
L. Bai,
F. Marumo,
and
S. Sasaki.
cAMP-dependent phosphorylation stimulates water permeability of aquaporin-collecting duct water channel protein expressed in Xenopus oocytes.
J. Biol. Chem.
270:
10384-10387,
1995
37.
Lande, M. B.,
I. Jo,
M. L. Zeidel,
M. Somers,
and
H. W. Harris.
Phosphorylation of aquaporin-2 does not alter the membrane water permeability of rat papillary water channel-containing vesicles.
J. Biol. Chem.
271:
5552-5557,
1996
38.
Li, D.,
A. Aperia,
G. Celsi,
E. F. da Cruz e Silva,
P. Greengard,
and
B. Meister.
Protein phosphatase-1 in the kidney: evidence for a role in the regulation of medullary Na+-K+-ATPase.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
269:
F673-F680,
1995
39.
Liu, J. P.
Protein phosphorylation events in exocytosis and endocytosis.
Clin. Exp. Pharmacol. Physiol.
24:
611-618,
1997[ISI][Medline].
40.
Maeda, Y.,
Y. Terada,
H. Nonoguchi,
and
M. A. Knepper.
Hormone and autacoid regulation of cAMP production in rat IMCD subsegments.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
263:
F319-F327,
1992
41.
Marples, D.,
M. A. Knepper,
E. I. Christensen,
and
S. Nielsen.
Redistribution of aquaporin-2 water channels induced by vasopressin in rat kidney inner medullary collecting duct.
Am. J. Physiol. Cell Physiol.
269:
C655-C664,
1995[Abstract].
42.
Nadler, S. P.,
S. C. Hebert,
and
B. M. Brenner.
PGE2, forskolin, and cholera toxin interactions in rabbit cortical collecting tubule.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
250:
F127-F135,
1986[ISI][Medline].
43.
Nadler, S. P.,
J. A. Zimpelmann,
and
R. L. Hébert.
PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
262:
F229-F235,
1992
44.
Nielander, H. B.,
F. Onofri,
F. Valtorta,
G. Schiavo,
C. Montecucco,
P. Greengard,
and
F. Benfenati.
Phosphorylation of VAMP/synaptobrevin in synaptic vesicles by endogenous protein kinases.
J. Neurochem.
65:
1712-1720,
1995[ISI][Medline].
45.
Nielsen, S.,
C. L. Chou,
D. Marples,
E. I. Christensen,
B. K. Kishore,
and
M. A. Knepper.
Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane.
Proc. Natl. Acad. Sci. USA
92:
1013-1017,
1995[Abstract].
46.
Nielsen, S.,
S. R. DiGiovanni,
E. I. Christensen,
M. A. Knepper,
and
H. W. Harris.
Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney.
Proc. Natl. Acad. Sci. USA
90:
11663-11667,
1993[Abstract].
47.
Nielsen, S.,
D. Marples,
H. Birn,
M. Mohtashami,
N. O. Dalby,
M. Trimble,
and
M. Knepper.
Expression of VAMP2-like protein in kidney collecting duct intracellular vesicles. Colocalization with aquaporin-2 water channels.
J. Clin. Invest.
96:
1834-1844,
1995[ISI][Medline].
48.
Nishimoto, G.,
M. Zelenina,
D. Li,
M. Yasui,
A. Aperia,
S. Nielsen,
and
A. C. Nairn.
Arginine vasopressin stimulates phosphorylation of aquaporin 2 in rat renal tissue.
Am. J. Physiol. Renal Physiol.
276:
F254-F259,
1999
49.
Noland, T. D.,
C. E. Carter,
H. R. Jacobson,
and
M. D. Breyer.
PGE2 regulates cAMP production in cultured rabbit CCD cells: evidence for dual inhibitory mechanisms.
Am. J. Physiol. Cell Physiol.
263:
C1208-C1215,
1992
50.
Ohara, M.,
P. Y. Martin,
D. L. Xu,
J. St John,
T. A. Pattison,
J. K. Kim,
and
R. W. Schrier.
Upregulation of aquaporin 2 water channel expression in pregnant rats.
J. Clin. Invest.
101:
1076-1083,
1998
51.
Paajanen, H.,
K. Satokari,
P. Uotila,
and
M. Kormano.
Prostaglandin levels in human renal venous blood during renal arteriography.
Eur. J. Radiol.
6:
132-135,
1986[ISI][Medline].
52.
Popoli, M.,
A. Venegoni,
C. Vocaturo,
L. Buffa,
J. Perez,
E. Smeraldi,
and
G. Racagni.
Long-term blockade of serotonin reuptake affects synaptotagmin phosphorylation in the hippocampus.
Mol. Pharmacol.
51:
19-26,
1997
53.
Rubenstein, J. L.,
P. Greengard,
and
A. J. Czernik.
Calcium-dependent serine phosphorylation of synaptophysin.
Synapse
13:
161-172,
1993[ISI][Medline].
54.
Saboli, I.,
T. Katsura,
J. M. Verbavatz,
and
D. Brown.
The AQP2 water channel: effect of vasopressin treatment, microtubule disruption, and distribution in neonatal rats.
Membr. Biol.
143:
165-75,
1995[ISI][Medline].
55.
Schuster, V. L.
Mechanism of bradykinin, ADH, and cAMP interaction in rabbit cortical collecting duct.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
249:
F645-F653,
1985[ISI][Medline].
56.
Sulimovici, S.,
A. J. Olmer,
and
C. P. Carvounis.
Vasopressin stimulates translocation of protein kinase C in the toad urinary bladder.
Exp. Nephrol.
4:
159-165,
1996[ISI][Medline].
57.
Terris, J.,
C. A. Ecelbarger,
D. Marples,
M. A. Knepper,
and
S. Nielsen.
Distribution of aquaporin-4 water channel expression within rat kidney.
Am. J. Physiol. Renal Fluid Electrolyte Physiol.
269:
F775-F785,
1995
58.
Tumlin, J. A.
Expression and function of calcineurin in the mammalian nephron: physiological roles, receptor signaling, and ion transport.
Am. J. Kidney Dis.
30:
884-895,
1997[ISI][Medline].
59.
Yamamoto, T.,
S. Sasaki,
K. Fushimi,
K. Kawasaki,
E. Yaoita,
K. Oota,
Y. Hirata,
F. Marumo,
and
I. Kihara.
Localization and expression of a collecting duct water channel, aquaporin, in hydrated and dehydrated rats.
Exp. Nephrol.
3:
193-201,
1995[ISI][Medline].