Редактирование: AQP2

Aquaporin-2 (AQP-2) (ADH water channel) (Aquaporin-CD) (AQP-CD) (Collecting duct water channel protein) (WCH-CD) (Water channel protein for renal collecting duct)

==Publications==

{{medline-entry
|title=A bell-shaped pattern of urinary aquaporin-2-bearing extracellular vesicle release in an experimental model of nephronophthisis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31074077
|abstract=The DBA/2-FG pcy (pcy) mouse is a model of human nephronophthisis, a recessive cystic kidney disease. Renal expression of aquaporin-2 ([[AQP2]]), a water channel protein, has been shown to be altered in pcy mice. However, the relationship between the renal expression and its release in urinary extracellular vesicles (uEV-[[AQP2]]), which account for most urinary [[AQP2]], in pcy mice has remained largely unknown. In this study, we examined age-related alterations of this relationship in pcy mice. In comparison with control mice, pcy mice after the age of 14 weeks showed defective urinary concentration ability with an increase in urinary volume. Interestingly, the release of uEV-[[AQP2]] increased progressively up to the age of 16 weeks, but at 21 weeks the release did not significantly differ from that in control mice (i.e., a bell-shaped pattern was evident). Similar results were obtained for uEV marker proteins, including tumor susceptibility gene 101 (TSG101) protein and apoptosis-linked gene 2-interacting protein X (Alix). Immunoblot analysis revealed that renal [[AQP2]] expression increased progressively from 11 weeks, and immunohistochemistry showed that this increase was possibly due to an increase in the number of [[AQP2]]-positive cells. Analysis of mRNAs for seven types of AQP expressed in the kidney supported this notion. These data suggest that the level of uEV-[[AQP2]] does not simply mirror the renal expression of [[AQP2]] and that the altered release of uEV-[[AQP2]] in pcy mice depends on the numbers of both renal [[AQP2]]-positive cells and EVs released into the urine.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Calcium-Binding Proteins
* DNA-Binding Proteins
* Disease Models, Animal
* Endosomal Sorting Complexes Required for Transport
* Extracellular Vesicles
* Gene Expression Regulation
* Kidney
* Kidney Diseases, Cystic
* Mice, Inbred DBA
* Mice, Mutant Strains
* RNA, Messenger
* Transcription Factors
|keywords=* Aquaporin-2
* pcy mice
* polycystic kidney disease
* urinary extracellular vesicles (exosomes)
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509436
}}
{{medline-entry
|title=Nitric oxide and [[AQP2]] in hypothyroid rats: a link between aging and water homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23706747
|abstract=Hypothyroid state and aging are associated with impairment in water reabsorption and changes in aquaporin water channel type 2 ([[AQP2]]). Nitric oxide (NO) is involved in [[AQP2]] trafficking to the apical plasma membrane in medullary collecting duct cells. The purpose of this study was to investigate whether aging and hypothyroidism alter renal function, and whether medullary NO and [[AQP2]] are implicated in maintaining water homeostasis. Sprague-Dawley rats aged 2 and 18months old were treated with 0.02% methimazole (w/v) during 28days. Renal function was examined and NO synthase (NOS) activity ([(14)C (U)]-L-arginine to [(14)C (U)]-L-citrulline assays), NOS, caveolin-1 and -3 and [[AQP2]] protein levels were determined in medullary tissue (Western blot). Plasma membrane fraction and intracellular vesicle fraction of [[AQP2]] were evaluated by Western blot and immunohistochemistry. A divergent response was observed in hypothyroid rats: while young rats exhibited polyuria with decreased medullary NOS activity, adult rats exhibited a decrease in urine output with increased NOS activity. [[AQP2]] was increased with hypothyroidism, but while young rats exhibited increased [[AQP2]] in plasma membrane, adult rats did so in the cytosolic site. Hypothyroidism contributes in a differential way to aging-induced changes in renal function, and medullary NO and [[AQP2]] would be implicated in maintaining water homeostasis.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Body Water
* Homeostasis
* Hypothyroidism
* Kidney
* Male
* Nitric Oxide
* Nitric Oxide Synthase
* Rats
* Rats, Sprague-Dawley
|keywords=* Aged
* Eut
* HR
* Hypo
* Intraperitoneal
* Ip
* MAP
* NO
* NOS
* Renal function
* T(4)
* TSH
* Thyroid hormones
* Water channel
* cav
* cav-1
* cav-3
* caveolin-1
* caveolin-3
* caveolins
* eNOS
* endothelial nitric oxide synthase
* euthyroid
* heart rate
* hypothyroid
* iNOS
* inducible nitric oxide synthase
* mean arterial pressure
* nNOS
* neuronal nitric oxide synthase
* nitric oxide
* nitric oxide synthase
* thyroid-stimulating hormone
* total thyroxine
|full-text-url=https://sci-hub.do/10.1016/j.metabol.2013.04.013
}}
{{medline-entry
|title=N-acetylcysteine attenuates renal alterations induced by senescence in the rat.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23183129
|abstract=The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n=6) or not (n=6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 ([[AQP2]]), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, [[AQP2]], and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, [[AQP2]], and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression.
|mesh-terms=* Acetylcysteine
* Age Factors
* Aging
* Animals
* Antioxidants
* Aquaporin 2
* Biomarkers
* Blotting, Western
* Cellular Senescence
* Cholesterol
* Ectodysplasins
* Glucuronidase
* Immunohistochemistry
* Inulin
* Kidney
* Male
* Membrane Transport Proteins
* Oxidative Stress
* Phosphates
* Rats
* Rats, Wistar
* Sodium-Potassium-Chloride Symporters
* Solute Carrier Family 12, Member 1
* Thiobarbituric Acid Reactive Substances
* Tumor Suppressor Protein p53

|full-text-url=https://sci-hub.do/10.1016/j.exger.2012.11.006
}}
{{medline-entry
|title=Age-related changes of aquaporin expression patterns in the postnatal rat retina.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23131425
|abstract=Previous studies revealed that the rat retina contains numerous membrane-located water channels, the aquaporins (AQPs). Protein expression patterns of [[AQP1]]-4, 6 and 9 were examined by immunohistochemistry. In the present study, we investigated the immunolocalization of [[AQP1]]-4, 6 and 9 during postnatal development in the rat retina and examined the effect of age on the tissue distribution of these channels. [[AQP1]], 3, 4, 6 and 9 showed gradually increased expression in rat retinas from postnatal week 1 to week 12, and decreased in the 40-week-old rat retinas. [[AQP2]] expression was barely seen in the first week in rat retinas and displayed a significant increase from week 1 to week 4, however no significant alteration of [[AQP2]] was observed after 4weeks of development. [[AQP1]] and 4 immunoreactivities were present in the inner limiting membrane (ILM), the ganglion cell layer (GCL), inner nuclear layer (INL) and retinal pigment epithelium ([[RPE]]) in the 4-, 12- and 40-week-old rat retinas. The [[RPE]], OLM and ILM showed a remarkable expression of [[AQP1]]-4, 6 and 9 in the 4, 12 and 40-week-old rat retinas. The reduced expression of AQPs in aged rat retinas may indicate the involvement of AQPs in the pathogenesis of age-related retinal diseases.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Aquaporins
* Gene Expression Profiling
* Gene Expression Regulation, Developmental
* Immunohistochemistry
* Rats
* Rats, Wistar
* Retina

|full-text-url=https://sci-hub.do/10.1016/j.acthis.2012.09.013
}}
{{medline-entry
|title=Age-related changes in expression in renal AQPs in response to congenital, partial, unilateral ureteral obstruction in rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22028046
|abstract=Previously we demonstrated that neonatally induced partial unilateral ureteral obstruction (PUUO) in rats is associated with changes in the abundance of renal acid-base transporters that were paralleled by reduction in renal functions dependent on the severity and duration of obstruction. The aim of the present study was to identify whether changes in renal aquaporin abundance are age-dependent. Semiquantitative immunoblotting and immunohistochemistry were used to examine the changes in abundance of [[AQP1]], [[AQP2]], p-S256[[AQP2]] ([[AQP2]] phosphorylated at consensus site Ser(256)) and [[AQP3]] in the kidneys of rats with neonatally induced PUUO within the first 48 h of life, and then monitored for 7 or 14 weeks. Protein abundance of [[AQP2]] and [[AQP3]] increased in both obstructed and non-obstructed kidneys 7 weeks after induction of neonatal PUUO (PUUO-7W). In contrast, [[AQP1]] and [[AQP2]] protein abundance in the obstructed kidney were reduced after 14 weeks of PUUO (PUUO-14W). Importantly, pS256-[[AQP2]] protein abundance was reduced in obstructed kidneys of both PUUO-7W and PUUO-14W. Immunohistochemistry confirmed the persistent pS256-[[AQP2]] downregulation in both PUUO-7W and PUUO-14W rats. The study shows that the protein abundance of [[AQP1]], [[AQP2]], and [[AQP3]] in the obstructed kidney is increased in PUUO-7W, which may be a compensatory phenomenon and reduced in PUUO-14W rats suggesting a time-/age-dependent dysregulation in response to PUUO. pS256-[[AQP2]] protein abundance is reduced consistent with obstruction-induced direct effects in the apical part of the collecting duct principal cells in response to PUUO.
|mesh-terms=* Age Factors
* Aging
* Animals
* Animals, Newborn
* Aquaporin 1
* Aquaporin 2
* Aquaporin 3
* Aquaporins
* Blotting, Western
* Disease Models, Animal
* Hydronephrosis
* Immunohistochemistry
* Kidney
* Male
* Phosphorylation
* Rats
* Ureteral Obstruction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223585
}}
{{medline-entry
|title=Altered expression of renal aquaporins and α-adducin polymorphisms may contribute to the establishment of salt-sensitive hypertension.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21451595
|abstract=Sodium-sensitive hypertension is caused by renal tubular dysfunction, leading to increased retention of sodium and water. Previous findings have suggested that single-nucleotide polymorphisms of the cytoskeletal protein, α-adducin, are associated with increased membrane expression of the Na/K pump and abnormal renal sodium transport in Milan hypertensive strain (MHS) rats and in humans. However, the possible contribution of renal aquaporins (AQPs) to water retention remains undefined in MHS rats. Kidneys from MHS rats were analyzed and compared with those from age-matched Milan normotensive strain (MNS) animals by quantitative-PCR, immunoblotting, and immunoperoxidase. Endocytosis assay was performed on renal cells stably expressing [[AQP4]] and co-transfected either with wild-type normotensive (NT) or with mutated hypertensive (HT) α-adducin. Semiquantitative immunoblotting revealed that [[AQP1]] abundance was significantly decreased only in HT MHS whereas [[AQP2]] was reduced in both young pre-HT and adult-HT animals. On the other hand, [[AQP4]] was dramatically upregulated in MHS regardless of the age. These results were confirmed by immunoperoxidase microscopy. Endocytosis assays clearly showed that the expression of mutated adducin strongly reduced the rate of constitutive [[AQP4]] endocytosis, thereby increasing its abundance at the plasma membrane. We provide here the first evidence that [[AQP1]], [[AQP2]], and [[AQP4]] are dysregulated in the kidneys of MHS animals. In particular, we provide evidence that α-adducin mutations may be responsible for [[AQP4]] upregulation. The downregulation of [[AQP1]] and [[AQP2]] and the upregulation of [[AQP4]] may be relevant for the onset and maintenance of salt-sensitive hypertension.
|mesh-terms=* Absorption
* Aging
* Animals
* Aquaporin 4
* Aquaporins
* Blood Pressure
* Calmodulin-Binding Proteins
* Disease Models, Animal
* Endocytosis
* Hypertension
* Kidney
* Male
* Polymorphism, Genetic
* Rats
* Rats, Mutant Strains
* Salt Tolerance
* Water

|full-text-url=https://sci-hub.do/10.1038/ajh.2011.47
}}
{{medline-entry
|title=Vasopressin-dependent upregulation of aquaporin-2 gene expression in aged rats with glucocorticoid deficiency.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19040709
|abstract=The study was undertaken to determine whether ageing affects kidney expression of the aquaporin-2 ([[AQP2]]) water channel in glucocorticoid-deficient rats. After adrenalectomy, 6- and 52-week-old Sprague-Dawley rats received aldosterone via osmotic minipumps (glucocorticoid-deficient rats). Aldosterone and dexamethasone were administered to control rats of the same age. An acute water load test verified impairment of water excretion in both young and aged rats with glucocorticoid deficiency, with a more serious impairment in the older rats. Despite the presence of hypoosmolality, non-suppressible release of arginine vasopressin ([[AVP]]) was particularly evident in the aged rats with glucocorticoid deficiency in comparison with the young rats. The expression levels of [[AQP2]] mRNA and protein were lower in the aged rats, with a particularly large reduction in [[AQP2]] protein expression. [[AQP2]] expression levels were significantly augmented in the glucocorticoid-deficient rats compared with the controls under both basal and water-loaded conditions. Acute water loading did not suppress expression of [[AQP2]] mRNA and protein, and the percentage increases in [[AQP2]] mRNA and protein expression vs. the respective controls were more pronounced in the 52-week-old glucocorticoid-deficient rats compared with the 6-week-old rats. The findings indicate that upregulation of [[AQP2]] expression is maintained dependent upon non-suppressible release of [[AVP]] in rats with glucocorticoid deficiency, and that [[AQP2]] plays a crucial role in persistent impairment of water excretion in aged rats with glucocorticoid deficiency.
|mesh-terms=* Adrenalectomy
* Aging
* Aldosterone
* Animals
* Aquaporin 2
* Arginine Vasopressin
* Dexamethasone
* Epithelial Sodium Channels
* Glucocorticoids
* Kidney
* Male
* Osmolar Concentration
* Rats
* Rats, Sprague-Dawley
* Sodium
* Up-Regulation
* Urine
* Vasopressins
* Water

|full-text-url=https://sci-hub.do/10.1111/j.1748-1716.2008.01938.x
}}
{{medline-entry
|title=Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18854434
|abstract=Mutations in aquaporin-2 ([[AQP2]]) that interfere with its cellular processing can produce autosomal recessive nephrogenic diabetes insipidus (NDI). Prior gene knock-in of the human NDI-causing [[AQP2]] mutation T126M produced mutant mice that died by age 7 days. Here, we used a novel "conditional gene knock-in" strategy to generate adult, [[AQP2]]-T126M mutant mice. Mice separately heterozygous for floxed wild-type [[AQP2]] and [[AQP2]]-T126M were bred to produce hemizygous mice, which following excision of the wild-type [[AQP2]] gene by tamoxifen-induced Cre-recombinase gave [[AQP2]](T126M/-) mice. [[AQP2]](T126M/-) mice were polyuric (9-14 ml urine/day) compared to [[AQP2]]( / ) mice (1.6 ml/day) and had reduced urine osmolality (400 vs. 1800 mosmol). Kidneys of [[AQP2]](T126M/-) mice expressed core-glycosylated [[AQP2]]-T126M protein in an endoplasmic reticulum pattern. Screening of candidate protein folding "correctors" in [[AQP2]]-T126M-transfected kidney cells showed increased [[AQP2]]-T126M plasma membrane expression with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG increased urine osmolality in [[AQP2]](T126M/-) mice by >300 mosmol but had no effect in [[AQP2]](-/-) mice. Kidneys of 17-AAG-treated [[AQP2]](T126M/-) mice showed partial rescue of defective [[AQP2]]-T126M cellular processing. Our results establish an adult mouse model of NDI and demonstrate partial restoration of urinary concentration function by a compound currently in clinical trials for other indications.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Base Sequence
* Cell Line
* Diabetes Insipidus, Nephrogenic
* Disease Models, Animal
* Dogs
* Gene Knock-In Techniques
* HSP90 Heat-Shock Proteins
* Mice
* Mice, Transgenic
* Mutation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630791
}}
{{medline-entry
|title=Hypovolemic state: involvement of nitric oxide in the aged related alterations of aquaporins-2 abundance in rat kidney.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18502184
|abstract=To examine the effect of nitric oxide (NO) on the expression and/or localization of inner medulla collecting duct aquaporin-2 water channel ([[AQP2]]) in young and adult hemorrhaged anesthetized rats. Rats of 2 (young) and 12 mo (adult) old (n=15) were divided into: Sham animals with and without NG-nitro-l-arginine methyl ester (L-NAME) treatment (S L-NAME and S); hemorrhaged animals (20% blood loss) with and without L-NAME (H L-NAME and H). Mean arterial pressure (MAP) was continuously monitored and [[AQP2]] expression and inmunolocalization were evaluated at 120 min after bleeding. L-NAME blunted the hypotension induced by hemorrhage at 120 min in young (106 /-2 mm Hg) and adult (103 /-4 mm Hg) rats. [[AQP2]] expression increased after bleeding in young (from 22 to 50 densitometric units) and adult rats (from 15 to 30 densitometric units). Pretreatment with L-NAME enhanced this effect, being this rise lower in adult than young animals (young: 318%, adult: 233%). Electron microscopy showed that [[AQP2]] labeling increased after withdrawal, being the number of gold particles smaller in adult than young animals in the inner medulla. L-NAME enhanced this effect. NOS activity decreases [[AQP2]] expression/traffick in the inner collecting duct principal cells in response to hemorrhage and this effect is lower with aging.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Blood Pressure
* Blotting, Western
* Enzyme Inhibitors
* Hemorrhage
* Hypovolemia
* Immunohistochemistry
* Kidney
* Male
* Microscopy, Immunoelectron
* NG-Nitroarginine Methyl Ester
* Nitric Oxide
* Nitric Oxide Synthase
* Rats
* Rats, Sprague-Dawley
* Water

|full-text-url=https://sci-hub.do/10.1016/j.vph.2008.04.001
}}
{{medline-entry
|title=Aquaporin-2 downregulation in kidney medulla of aging rats is posttranscriptional and is abolished by water deprivation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18367658
|abstract=Aging kidney is associated in humans and rodents with polyuria and reduced urine concentrating ability. In senescent female WAG/Rij rats, this defect is independent of arginine-vasopressin ([[AVP]])/V(2) receptor/cAMP pathway. It has been attributed to underexpression and mistargeting of aquaporin-2 ([[AQP2]]) water channel in the inner medullary collecting duct (IMCD). We showed previously that dD[[AVP]] administration could partially correct this defect. Since [[AQP2]] can also be regulated by [[AVP]]-independent pathways in water deprivation (WD), we investigated [[AQP2]] and phosphorylated [[AQP2]] (p-[[AQP2]]) regulation in thirsted adult (10 mo old) and senescent (30 mo old) female WAG/Rij rats. Following 2-day WD, urine flow rate decreased and urine osmolality increased in both groups. However, in agreement with significantly lower cortico-papillary osmotic gradient with aging, urine osmolality remained lower in senescent animals. WD induced sixfold increase of plasma [[AVP]] in all animals which, interestingly, did not result in higher papillary cAMP level. Following WD, [[AQP2]] and p-[[AQP2]] expression increased hugely in 10- and 30-mo-old rats and their mistargeting in old animals was corrected. Moreover, the age-related difference in [[AQP2]] regulation was abolished after WD. To further investigate the mechanism of [[AQP2]] underexpression with aging, [[AQP2]] mRNA was quantified by real-time RT-PCR. In the outer medulla, preservation of [[AQP2]] protein expression was achieved through increased [[AQP2]] mRNA level in senescent rats. In the IMCD, no change in [[AQP2]] mRNA was detected with aging but [[AQP2]] protein expression was markedly lower in 30-mo-old animals. In conclusion, there is a posttranscriptional downregulation of [[AQP2]] with aging, which is abolished by WD.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Cyclic AMP
* Cyclic GMP
* Down-Regulation
* Female
* Kidney Concentrating Ability
* Kidney Medulla
* Osmolar Concentration
* Phosphorylation
* RNA Processing, Post-Transcriptional
* RNA, Messenger
* Rats
* Rats, Inbred Strains
* Reverse Transcriptase Polymerase Chain Reaction
* Water Deprivation
* Water-Electrolyte Balance

|full-text-url=https://sci-hub.do/10.1152/ajprenal.00437.2007
}}
{{medline-entry
|title=Hyaluronan-related limited concentration by the immature kidney.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16140463
|abstract=The limited renal concentration performance by the immature kidney traditionally is thought to be attributed to blunted renal response to arginine vasopressin ([[AVP]]) and medullary hypotonicity. The diminished [[AVP]]-dependent osmotic water permeability of the collecting duct is the result of decreased [[AVP]] binding and adenylate cyclase activation, and low expression of aquaporin-2 ([[AQP2]]) mRNA and low levels of [[AQP2]] protein. Moreover, the immature kidney fails to establish deep cortico-papillary osmotic gradient because of structural immaturity, limited solute transport and increased medullary blood flow. Based on indirect clinical and experimental evidences this article puts forward a hypothesis that during perinatal period the abundant hyaluronan (HA) content in the renomedullary interstitium has a primary role in antagonizing water reabsorption and limiting concentration performance. Hydration-related alterations in renal HA appears to be mediated by antidiuretic hormone. The concept of HA-mediated renal water transport may imply that interfering selectively with renal HA metabolism may provide a new therapeutic approach to promote diuresis or antidiuresis, respectively, according to the elevation or reduction in renomedullary HA.
|mesh-terms=* Aging
* Animals
* Body Water
* Evidence-Based Medicine
* Humans
* Hyaluronic Acid
* Kidney
* Models, Biological
* Urination
* Water-Electrolyte Balance

|full-text-url=https://sci-hub.do/10.1016/j.mehy.2005.02.048
}}
{{medline-entry
|title=Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15213068
|abstract=Renal concentrating ability is known to be impaired with aging. The antidiuretic hormone [[AVP]] plays an important role in renal water excretion by regulating the membrane insertion and abundance of the water channel aquaporin-2 ([[AQP2]]); this effect is primarily mediated via the V2 subtype of the [[AVP]] receptor (V2R). This study evaluated the hypothesis that decreased renal sensitivity to [[AVP]], with subsequent altered renal [[AQP2]] expression, contributes to the reduced urinary concentrating ability with aging. Our results show that under baseline conditions, urine osmolality is significantly lower in aged Fischer 344 and Brown-Norway F1 hybrid (F344BN) rats despite equivalent plasma [[AVP]] concentrations as in young rats. Levels of kidney V2R mRNA expression and [[AQP2]] abundances were also significantly decreased in aged F344BN rats, as was [[AQP2]] immunostaining in collecting duct cells. In response to moderate water restriction, urine osmolality increased by significantly lesser amounts in aged F344BN rats compared with young rats despite similar increases in plasma [[AVP]] levels. Moderate water restriction induced equivalent relative increases in renal [[AQP2]] abundances in all age groups but resulted in significantly lower abundances in total kidney [[AQP2]] protein in aged compared with young F344BN rats. These results therefore demonstrate a functional impairment of renal concentrating ability in aged F344BN rats that is not due to impaired secretion of [[AVP]] but rather appears to be related to impaired responsiveness of the kidney to [[AVP]] that is secondary, at least in part, to a downregulation of renal V2R expression and [[AQP2]] abundance.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Aquaporins
* Arginine Vasopressin
* Dehydration
* Down-Regulation
* Gene Expression
* Immunohistochemistry
* Kidney
* Kidney Concentrating Ability
* Male
* RNA, Messenger
* Rats
* Rats, Inbred F344
* Receptors, Vasopressin
* Urine
* Water-Electrolyte Balance

|full-text-url=https://sci-hub.do/10.1152/ajprenal.00403.2003
}}
{{medline-entry
|title=[Vasopressin-dependent water permeability of the basolateral membrane of the kidney outer medullary collecting duct in postnatal ontogenesis in rats].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/14502981
|abstract=Kidneys of new-born animals are resistant to arginine vasopressin ([[AVP]]). The ability of the hormone to regulate water permeability of the collecting duct can be seen from weaning period, probably due to the maturation of the intracellular signaling pathway. The purpose of the present work was to investigate the effect of V2 receptor agonist dD[[AVP]] on the water permeability of OMCD basolateral membrane in 10-, 22- and 60-day old Wistar rats. We also estimated ontogenetic gene expression of [[AQP2]], [[AQP3]], [[AQP4]] and V2 receptor. Osmotic water permeability (Pf) of the basolateral membrane of microdissected OMCD was measured under control conditions and after incubation with the agonist V2 receptor desmopressin (dD[[AVP]]; 10(-7) M). Water permeability in 10- and 22-day old rats under control conditions were significantly higher than in adults. Desmopressin stimulated significant increase of this parameter in 22-day old pups (Pf = = 125  /- 4.85; Pf = 174  /- 8.2 microns/s, p < 0.001) and adult rats (Pf = 100.5  /- 7.38; Pf = 178.8  /- 9.54 microns/s, p < 0.001). Osmotic water permeability of the OMCD basolateral membrane in 10-day old rats does not depend on dD[[AVP]] (Pf = 172.5  /- 23.8; Pf = 164.8  /- 34 microns/s). With the RT-PCR, we observed a gradual increase of [[AQP2]] and V2 receptor genes expression during postnatal ontogenesis. The gene expression of [[AQP3]] and [[AQP4]] remained unchanged during postnatal ontogenesis. In general, the water permeability of the OMCD basolateral membrane of rats can be stimulated by [[AVP]] since the 22nd day of postnatal life. The water permeability of the OMCD basolateral membrane under control conditions gradually decreased during postnatal development, while gene expression of [[AQP3]] and [[AQP4]] was unchanged. The mechanism of this decrease remains to be established.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Aquaporin 6
* Aquaporins
* Cell Membrane Permeability
* Deamino Arginine Vasopressin
* Female
* Kidney Medulla
* Kidney Tubules, Collecting
* Male
* Osmosis
* Rats
* Rats, Wistar
* Receptors, Vasopressin
* Renal Agents
* Water


}}
{{medline-entry
|title=Expression and localization of aquaporins, members of the water channel family, during development of the rat submandibular gland.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12838423
|abstract=The expression and localization of aquaporins ([[AQP1]]-[[AQP5]]), members of the water channel family, in the developing rat submandibular gland were analysed using RT-PCR, Northern blotting and immunohistochemistry to explore their relation to the development of this salivary gland. RT-PCR analysis revealed unique expression patterns of each AQP. [[AQP1]] was expressed constitutively during prenatal development, whereas the expression of [[AQP5]] became more intense in the course of development from embryonic day 16.5 (E16) to E20. These expression patterns concurred with the results of Northern blot analysis. [[AQP3]] and [[AQP4]] mRNAs in the prenatal development were not detected in Northern blots, although they were detected by RT-PCR. During postnatal development, [[AQP5]] and [[AQP1]] mRNAs were expressed continuously, but no message for [[AQP3]] or [[AQP4]] was detected. [[AQP2]] mRNA was not detected during either prenatal or postnatal development in this tissue. Immunohistochemical studies revealed that [[AQP5]] was first localized at the apical membrane of proacinar cells at E18, and then became clearly distributed at the apical membrane of acinar cells in accordance with the differentiation and establishment of the mature acini. In addition, some vasculature also showed immunoreactivity for [[AQP5]]. [[AQP1]] was immunolocalized in the blood vessels, including capillaries, of the gland throughout development. These observations suggest the existence of transcriptional regulation of rat [[AQP5]], which is one of the most probable regulators of saliva production and secretion, during the establishment of the functional submandibular salivary gland.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Aquaporins
* Biological Transport, Active
* Blotting, Northern
* Body Water
* Female
* Immunohistochemistry
* Molecular Sequence Data
* Pregnancy
* RNA
* RNA, Antisense
* Rats
* Rats, Sprague-Dawley
* Reverse Transcriptase Polymerase Chain Reaction
* Sodium-Potassium-Exchanging ATPase
* Submandibular Gland

|full-text-url=https://sci-hub.do/10.1007/s00424-003-1109-9
}}
{{medline-entry
|title=Correction of age-related polyuria by dDAVP: molecular analysis of aquaporins and urea transporters.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12388383
|abstract=Senescent female WAG/Rij rats exhibit polyuria without obvious renal disease or defects in vasopressin plasma level or V(2) receptor mRNA expression. Normalization of urine flow rate by 1-desamino-8-d-arginine vasopressin (dDAVP) was investigated in these animals. Long-term dDAVP infusion into 30-mo-old rats reduced urine flow rate and increased urine osmolality to levels comparable to those in control 10-mo-old rats. The maximal urine osmolality in aging rat kidney was, however, lower than that in adult kidney, despite supramaximal administration of dDAVP. This improvement involved increased inner medullary osmolality and urea sequestration. This may result from upregulation of UT-A1, the vasopressin-regulated urea transporter, in initial inner medullary collecting duct (IMCD), but not in terminal IMCD, where UT-A1 remained low. Expression of UT-A2, which contributes to medullary urea recycling, was greatly increased. Regulation of IMCD aquaporin (AQP)-2 ([[AQP2]]) expression by dDAVP differed between adult and senescent rats: the low [[AQP2]] abundance in senescent rats was normalized by dDAVP infusion, which also improved targeting of the channel; in adult rats, [[AQP2]] expression was unaltered, suggesting that IMCD [[AQP2]] expression is not regulated by dDAVP directly. Increased [[AQP3]] expression in senescent rats may also be involved in improved urine-concentrating capacity owing to higher basolateral water and urea reabsorption capacity.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Aquaporin 3
* Aquaporin 6
* Aquaporins
* Carrier Proteins
* Corticosterone
* Deamino Arginine Vasopressin
* Female
* Gene Expression
* Kidney Medulla
* Membrane Glycoproteins
* Membrane Transport Proteins
* Nitric Oxide Synthase
* Osmolar Concentration
* Polyuria
* Rats
* Rats, Inbred Strains
* Renal Agents
* Urea
* Urine
* Water-Electrolyte Balance

|full-text-url=https://sci-hub.do/10.1152/ajprenal.00167.2002
}}
{{medline-entry
|title=Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11704564
|abstract=The mechanisms underlying the prevention of age-related polyuria by chronic food restriction were investigated in female WAG/Rij rats. The decreased osmolality of renal papilla observed in senescent rats was not corrected by food restriction. A reduced urea content in the inner medulla of senescent rats, fed ad libitum or food-restricted, was suggested by the marked decrease in expression of UT-A1 and UT-B1 urea transporters. Aquaporin-2 ([[AQP2]]) downregulation in the inner medulla of senescent rats was partially prevented by food restriction. Both [[AQP2]] and the phosphorylated form of [[AQP2]] (p-[[AQP2]]), the presence of which was diffuse within the cytoplasm of collecting duct principal cells in normally fed senescent rats, were preferentially targeted at the apical region of the cells in food-restricted senescent animals. Plasma vasopressin ([[AVP]]) was similar in 10- and 30-mo-old rats fed ad libitum, but was doubled in food-restricted 30-mo-old rats. This study indicates that 1) kidney aging is associated with a marked decrease in [[AQP2]], UT-A1, and UT-B1 expression in the inner medulla and a reduced papillary osmolality; and 2) the prevention of age-related polyuria by chronic food restriction occurs through an improved recruitment of [[AQP2]] and p-[[AQP2]] to the apical membrane in inner medulla principal cells, permitted by increased plasma [[AVP]] concentration.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Aquaporin 6
* Aquaporins
* Carrier Proteins
* Cell Polarity
* Eating
* Female
* Kidney
* Kidney Medulla
* Kidney Tubules
* Membrane Glycoproteins
* Membrane Transport Proteins
* Osmolar Concentration
* Phosphorylation
* Polyuria
* Protein Transport
* Rats
* Urine
* Vasopressins
* Water-Electrolyte Imbalance

|full-text-url=https://sci-hub.do/10.1152/ajprenal.0139.2001
}}
{{medline-entry
|title=Aquaporin 9 expression along the male reproductive tract.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11466204
|abstract=Fluid movement across epithelia lining portions of the male reproductive tract is important for modulating the luminal environment in which sperm mature and reside, and for increasing sperm concentration. Some regions of the male reproductive tract express aquaporin (AQP) 1 and/or [[AQP2]], but these transmembrane water channels are not detectable in the epididymis. Therefore, we used a specific antibody to map the cellular distribution of another AQP, [[AQP9]] (which is permeable to water and to some solutes), in the male reproductive tract. [[AQP9]] is enriched on the apical (but not basolateral) membrane of nonciliated cells in the efferent duct and principal cells of the epididymis (rat and human) and vas deferens, where it could play a role in fluid reabsorption. Western blotting revealed a strong 30-kDa band in brush-border membrane vesicles isolated from the epididymis. [[AQP9]] is also expressed in epithelial cells of the prostate and coagulating gland where fluid transport across the epithelium is important for secretory activity. However, it was undetectable in the seminal vesicle, suggesting that an alternative fluid transport pathway may be present in this tissue. Intracellular vesicles in epithelial cells along the reproductive tract were generally poorly stained for [[AQP9]]. Furthermore, the apical membrane distribution of [[AQP9]] was unaffected by microtubule disruption. These data suggest that [[AQP9]] is a constitutively inserted apical membrane protein and that its cell-surface expression is not acutely regulated by vesicular trafficking. [[AQP9]] was detectable in the epididymis and vas deferens of 1-wk postnatal rats, but its expression was comparable with adult rats only after 3--4 wk. [[AQP9]] could provide a route via which apical fluid and solute transport occurs in several regions of the male reproductive tract. The heterogeneous and segment-specific expression of [[AQP9]] and other aquaporins along the male reproductive tract shown in this and in our previous studies suggests that fluid reabsorption and secretion in these tissues could be locally modulated by physiological regulation of AQP expression and/or function.
|mesh-terms=* Aging
* Animals
* Aquaporins
* Blotting, Western
* Colchicine
* Electrophoresis, Polyacrylamide Gel
* Epididymis
* Fluorescent Antibody Technique, Indirect
* Immunohistochemistry
* Kidney
* Male
* Microscopy, Immunoelectron
* Microvilli
* Rats
* Rats, Sprague-Dawley
* Vas Deferens

|full-text-url=https://sci-hub.do/10.1095/biolreprod65.2.384
}}
{{medline-entry
|title=Postnatal disappearance of type A intercalated cells in carbonic anhydrase II-deficient mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11420910
|abstract=Despite chronic acidosis, collecting ducts in adult carbonic anhydrase II-deficient ([[CAD]] mice) are depleted of intercalated cells, including those of type A, which are acid-secreting cells. We hypothesized that this depletion could occur during postnatal development. Principal cells were identified by immunofluorescence using an antibody to rat aquaporin-2 (AQP-2), and type A intercalated cells using an antibody specific for anion exchanger (AE1). In [[CAD]] mice the proportion of [[AQP2]]-positive cells, normal at 11 days, increased progressively in the cortical (CCD) and outer medullary collecting duct (OMCD), to reach almost 100% in the OMCD in adults. The percentage of AE1-positive cells in the OMCD of [[CAD]] mice decreased by half by 6 weeks of age and further by adulthood. In controls, however, the proportion of [[AQP2]]-positive cells and that of AE1-positive cells in the OMCD remained stable after 10 days of age. AE1-positive cells accounted for the majority of intercalated cells in the OMCD. The mechanisms leading to selective postnatal cell depletion in the collecting duct in [[CAD]] mice remain to be determined.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Antiporters
* Aquaporin 2
* Aquaporin 6
* Aquaporins
* Carbonic Anhydrases
* Chloride-Bicarbonate Antiporters
* Fluorescent Antibody Technique
* Heterozygote
* Kidney Tubules, Collecting
* Male
* Mice
* Microscopy, Fluorescence

|full-text-url=https://sci-hub.do/10.1007/s004670100565
}}
{{medline-entry
|title=Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2) vasopressin receptor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10894796
|abstract=The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9  /- 0.3 ml/24 h and 2,511  /- 54 mosmol/kgH(2)O in adult rats and 12.8  /- 0.8 ml/24 h and 1,042  /- 44 mosmol/kgH(2)O in senescent animals. Vasopressin V(2) receptor mRNA did not significantly differ between 10 and 30 mo, and [(3)H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 ([[AQP2]]) and -3 ([[AQP3]]) expression was downregulated by 80 and 50%, respectively, and [[AQP2]] was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of [[AQP2]] and [[AQP3]] expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Aquaporin 3
* Aquaporin 6
* Aquaporins
* Binding Sites
* Body Weight
* Cell Membrane
* Cyclic AMP
* Down-Regulation
* Drinking
* Eating
* Female
* Fluorescent Antibody Technique, Indirect
* Kidney
* Kidney Medulla
* Kidney Tubules
* Osmolar Concentration
* Polyuria
* RNA, Messenger
* Rats
* Rats, Inbred Strains
* Receptors, Vasopressin
* Vasopressins

|full-text-url=https://sci-hub.do/10.1152/ajprenal.2000.279.1.F144
}}
{{medline-entry
|title=Age-associated decrease in response of rat aquaporin-2 gene expression to dehydration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9496709
|abstract=It is well known that urine-concentrating ability decreases with aging and that this decreasing ability results from a reduced sensitivity of the renal collecting duct to arginine vasopressin ([[AVP]]). [[AVP]] regulates the water channel (aquaporin-2:[[AQP2]]) through V2 receptors and increases the water permeability of the collecting duct. To elucidate the mechanism of change with aging in urine-concentrating ability, we investigated the change of V2 receptor and [[AQP2]] mRNA expression in young (8-week-old) and older (7-month-old) rats after dehydration for 2 days. After dehydration, plasma [[AVP]] levels in older rats were higher than young rats, and urinary osmolality in older rats was lower than young rats. By Northern blot analysis, there was no significant difference between young and older rats in both V2 receptor and [[AQP2]] mRNA expression before dehydration. After dehydration, V2 receptor mRNA expression in young and older rats decreased in the same degree, suggesting the downregulation of V2 receptors may occur in the mRNA level. Northern blot analysis and in situ hybridization histochemistry showed that [[AQP2]] mRNA expression increased and the increased expression in older rats was less than in young rats. The present study suggests the reduced response of [[AQP2]] mRNA expression to dehydration, observed in 7-month-old rats, might be partially responsible for the decreasing urine-concentrating ability with aging.
|mesh-terms=* Aging
* Animals
* Aquaporin 2
* Aquaporin 6
* Aquaporins
* Dehydration
* Gene Expression Regulation
* Ion Channels
* Rats

|full-text-url=https://sci-hub.do/10.1016/s0024-3205(98)00004-6
}}
{{medline-entry
|title=Expression of AQP family in rat kidneys during development and maturation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9124396
|abstract=The mRNA expression and localization of the aquaporin (AQP) family in rat kidney were examined by ribonuclease protection assay and immunohistochemistry. [[AQP1]], [[AQP2]], [[AQP3]], and [[AQP4]] mRNA were hardly detectable in 16-day gestation fetuses. [[AQP1]] mRNA was explosively expressed at 1 wk, keeping the level throughout life. [[AQP2]] mRNA expression was apparently noticed in 18-day fetuses and was enhanced gradually with age to reach a plateau at 4 wk. [[AQP3]] and [[AQP4]] mRNA expression was significantly found at birth but was not changed remarkably thereafter. [[AQP2]] protein appeared first at the apical side of collecting duct cells in 18-day fetuses. The staining intensity at the site increased with age, and basolateral staining was added in adult rats. [[AQP3]] was distinctly demonstrated at the basolateral side of collecting duct cells after birth, and the staining intensity was almost stable throughout life. The progressive induction of [[AQP2]] expression in the first 4 wk after birth is presumed to contribute to the maturation of urinary concentrating capacity during the kidney development.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Embryo, Mammalian
* Embryonic and Fetal Development
* Immunohistochemistry
* Ion Channels
* Kidney
* RNA, Messenger
* Rats
* Rats, Inbred WKY
* Water

|full-text-url=https://sci-hub.do/10.1152/ajprenal.1997.272.2.F198
}}
{{medline-entry
|title=Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8760258
|abstract=Aquaporin-1 ([[AQP1]]), located in proximal tubules (PT) and descending thin limbs of Henle ([[DTL]]), and aquaporin-2 ([[AQP2]]), located in collecting ducts (CD), are channels involved in water transport across renal tubule epithelia. Using antibodies against [[AQP1]] and [[AQP2]], we here show expression of [[AQP1]] and [[AQP2]] in normal human developing and adult kidneys and in autosomal dominant polycystic kidney disease (ADPKD). Unlike in rats, [[AQP1]] and [[AQP2]] are expressed early during human nephrogenesis (12-wk gestation). [[AQP1]] was first seen in developing PT epithelia, predominantly in apical cell membranes, and, at 15 wk, was also detected in [[DTL]]. [[AQP2]] was seen in apical cell membranes of the branching ureteric bud and CD system from 12 wk and throughout development. In adult normal kidneys, [[AQP1]] was localized to apical and basolateral membrane domains of PT and [[DTL]], whereas [[AQP2]] was restricted to principal cells of CD. This distribution of [[AQP1]] and [[AQP2]] was also seen in early stage ADPKD, except that [[AQP1]] was mostly located in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of the cysts expressed either [[AQP1]] or [[AQP2]], but these two water channels were never colocalized in the same cyst. Western blot analysis showed maximal expression of [[AQP1]] and [[AQP2]] in normal adult kidneys, lower levels in fetal kidneys, and decreases associated with degree of cystic progression in ADPKD. These data 1) demonstrate specific, mutually exclusive localization of [[AQP1]] and [[AQP2]] in human fetal and adult kidneys; 2) show that both channels are expressed early during nephrogenesis; and 3) show that the mutual exclusivity of localization is maintained even into end-stage ADPKD.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Animals, Newborn
* Aquaporin 1
* Aquaporin 2
* Aquaporin 6
* Aquaporins
* Blood Group Antigens
* Blotting, Western
* Embryonic and Fetal Development
* Humans
* Immunohistochemistry
* Ion Channels
* Kidney
* Molecular Sequence Data
* Polycystic Kidney, Autosomal Dominant
* Rats
* Reference Values
* Staining and Labeling

|full-text-url=https://sci-hub.do/10.1152/ajprenal.1996.271.1.F169
}}