Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrogenic diabetes insipidus is a rare genetic disorder characterized by insensitivity of the distal nephron to the antidiuretic effect of arginine vasopressin. Two different molecular defects underlying this disease have so far been identified. Mutations in the gene encoding the vasopressin type-2 receptor cause the X-chromosomal form of the disease, whereas mutations in the gene encoding the vasopressin-dependent water channel aquaporin-2 are responsible for the autosomal recessive, and (in some cases) an autosomal dominant type of the disease. Functional analysis of naturally occurring mutations in the vasopressin type-2 receptor and aquaporin-2 have increased the insight into the structure and function of both proteins and have led to substantial progress in understanding the cellular mechanisms underlying the concentrating ability of the kidney. Some female carriers of a vasopressin type-2 receptor mutation may show complete manifestation of nephrogenic diabetes insipidus, probably as a result of skewed X-inactivation. The recent findings in nephrogenic diabetes insipidus research have considerable impact for diagnosis of and genetic counselling for this disease.
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PMID:Molecular and cellular defects in nephrogenic diabetes insipidus. 882 34

A cDNA was cloned from the epithelium of toad (Bufo marinas) urinary bladder, based on homology to the mammalian aquaporins (AQP). The cDNA [947 base pairs (bp), identified as AQP-t1] encoded a 272-amino acid protein with 76% identity to mammalian aquaporin-1 (AQP-1) and 88% identity to frog water channel FA-CHIP. AQP-t1 cDNA was nearly identical to a fragment of a nonfunctional cDNA cloned recently from toad bladder ["AQP-TB"; J. Siner, A. Paredes, C. Hosselet, T. Hammond, K. Strange, and H.W. Harris, Am. J. Physiol. 270 (Cell Physiol. 39): C372-C381, 1996], except for reading frame shifts at bp 253, 264, and 682, two single amino acid deletions, a different 3'-coding sequence downstream from bp 786, and a different 5' sequence upstream from bp 9. Water permeability (Pf) in Xenopus laevis oocytes expressing AQP-t1 cRNA was strongly increased from (0.83 +/- 0.06) x 10(-3) cm/s (water-injected control) to (17 +/- 4) x 10(-3) cm/s, with 80% inhibition by 0.3 mM HgCl2; glycerol and urea permeabilities were not increased. Northern blot analysis showed a single AQP-t1 mRNA of 2.8 kb in eye > lung > urinary bladder > skin > stomach approximately heart, brain, and intestine. AQP-t1 mRNA expression was not changed by a 3-day dehydration of toads or an 8-h stimulation of Pf in isolated bladders by forskolin. These results indicate that the epithelium of toad urinary bladder expresses a functional homologue of AQP-1 and FA-CHIP that is probably not vasopressin regulated.
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PMID:cDNA cloning of a functional water channel from toad urinary bladder epithelium. 894 54

The aquaporins are molecular water channels that mediate transcellular water transport across water-permeable epithelia. To investigate the cause of the concentrating defect in the nephrotic syndrome, immunoblotting using membrane fractions from inner medulla was utilized to assess the level of expression of four aquaporin water channels in vehicle-treated versus puromycin aminonucleoside (PAN)-treated rats. Scanning electron microscopy demonstrating loss of glomerular foot processes and measurements of urinary protein excretion confirmed the efficacy of the PAN treatment. In rats receiving PAN, there was an increase in plasma vasopressin, without a change in plasma sodium concentration. Inner medullary tissue hypertonicity was sustained in PAN-treated rats while the urinary osmolality was low, pointing to defective osmotic equilibration across the collecting ducts in PAN-nephrosis. Among collecting duct aquaporins, there was an 87% decrease in aquaporin-2 expression and a 70% decrease in aquaporin-3 expression in the inner medulla, whereas aquaporin-4 expression was unaltered. Transmission electron microscopy of the inner medullary collecting ducts of PAN-treated rats showed normal-appearing cells. Thus, PAN-nephrosis is associated with an extensive downregulation of collecting duct water channel expression despite increased circulating vasopressin, providing an explanation for the concentrating defect associated with the nephrotic syndrome.
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PMID:Reduced renal medullary water channel expression in puromycin aminonucleoside--induced nephrotic syndrome. 901 44

In a normal adult subject, 12 liters of tubular urine with an osmolality of 100 mmol/kg exit per 24 hours from the loop of Henle. The antidiuretic hormone arginine-vasopressin increases the water permeability of the renal collecting ducts and induces the reabsorption of 11 liters of water: the final urinary osmolality is 1200 mmol/kg for a urinary flow rate of 1 litre per 24 hours. In nephrogenic diabetes insipidus the urine cannot be concentrated maximally. Congenital nephrogenic diabetes insipidus is secondary to either mutations in the AVPR2 gene (Xq28) that codes for the vasopressin antidiuretic (V2) receptor or to mutations in the AQP2 gene (12q13) that codes for the vasopressin dependent water channel. AVPR2 mutations are numerous and diverse: 72 different putative disease causing mutations in the AVPR2 gene have been reported in 102 unrelated families with X-linked nephrogenic diabetes insipidus. AQP2 mutations are rare. Nephrogenic diabetes insipidus could also be secondary to lithium or demeclocycline administration and to hypokaliemia. Some of these conditions are inducing, experimentally, a downregulation of aquaporin II. We encourage physicians who follow families with hereditary nephrogenic diabetes insipidus to recommend molecular genetic analysis because early diagnosis and treatment of infants can avert the physical and mental retardation associated with episodes of dehydration.
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PMID:[Pathological aspects of water transport in the collecting ducts]. 901 68

The purpose of this review is to illustrate the application of molecular methodologies to the investigation of a fundamentally integrative problem in renal physiology, namely, the mechanism of regulation of water excretion by the kidney and the concomitant concentration of solutes in the urine. A new revolution in renal physiology is occurring as new research tools have become available as a result of the cloning of cDNAs for many of the major transporters and receptors in the renal medulla. Among the important renal medullary transporters are the aquaporin water channels, which mediate the osmotic water transport across renal medullary epithelia. One of these water channels, aquaporin-2, has been shown to be the target for short-term regulation of collecting duct water permeability by vasopressin. In addition, two collecting duct water channels, aquaporin-2 and aquaporin-3, are targets for long-term regulation by vasopressin through effects on the absolute expression levels of the water channel proteins. This review focuses on the mechanisms of both short- and long-term regulation of these water channels by vasopressin.
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PMID:Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. 903 43

The osmotic water permeability of epithelial cells of the inner medullary collecting duct of the kidney is regulated by antidiuretic hormone (ADH). ADH causes the insertion and removal of cytoplasmic vesicles containing the aquaporin (AQP-2) water channel protein which is recognized by multiple rabbit antipeptide antisera raised against amino acid sequences comprising its cytoplasmic carboxyl terminal. Immunoblots of rat kidney membrane fractions as well as human urine have all shown that AQP-2 is expressed exclusively by collecting duct cells and have identified a 29 kDa band (corresponding to the nonglycosylated AQP-2 protein), a broad 35-45 kDa band (corresponding to the mature glycosylated form of AQP-2 protein) and an additional immunoreactive 17 kDa band of unknown origin. We now report that the 17 kDa band identified by these anti-AQP-2 antisera is not an AQP-2 component but rather a denatured histone protein type H2A1. This binding of anti-AQP-2 antisera to denatured H2A1 present in protein samples derived from both kidney inner medulla and human urine is blocked specifically by preincubation of immunoblots with solutions containing the acidic protein gelatin.
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PMID:The 17 kDa band identified by multiple anti-aquaporin 2 antisera in rat kidney medulla is a histone. 905 2

To characterize the cyst-lining cells in human autosomal dominant polycystic kidney disease (ADPKD), we performed immunohistological studies with specific antibodies against human aquaporin-2 (AQP-2, the vasopressin-regulated water channel) and aquaporin-3 (AQP-3), which are expressed only in collecting duct cells in the normal kidney. The polycystic kidney samples were obtained from 2 hemodialysis patient at uninephrectomy. Immunohistochemical studies revealed two types of staining of cyst-lining cells. Approximately 30% of all the cysts were simultaneously immunostained by both antibodies. Among these AQP-positive cysts, more than 90% of the cysts were intensely stained, with well-polarized localization of AQP-2 and AQP-3. In fewer than 10% of AQP-positive cysts, by contrast, immunostaining for AQP-2 and AQP-3 was faint and no clearly polarized localization of the channels was observed. We examined the immunostaining in further detail by electron microscopy. Staining specific for AQP-2 was mainly observed in the apical membrane of cyst-lining cells. Moreover, staining specific for AQP-3 was observed in all of the AQP-2-positive cysts. It appeared unlikely that the variations in immunostaining observed under the light microscope had been induced by total disruption of water-channel polarity. The present study suggests that about 30% of the cysts in our cases of ADPKD were derived from the collecting duct cells and that the cyst-lining cells were well differentiated in terms of AQP expression.
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PMID:Expression and localization of the water channels in human autosomal dominant polycystic kidney disease. 945 14

The purpose of this study was to investigate whether escape from vasopressin-induced antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct.
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PMID:Role of renal aquaporins in escape from vasopressin-induced antidiuresis in rat. 910 29

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.
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PMID:Upregulation of aquaporin-2 water channel expression in chronic heart failure rat. 911 93

Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.
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PMID:Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. 914 44


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