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)

The longstanding puzzle of membrane water-permeability was advanced by discovery of a new class of proteins known as the "aquaporins" (AQPs). First identified in red blood cells, AQP1 was shown to function as a water channel when expressed in Xenopus oocytes or when pure AQP1 protein was reconstituted into synthetic membranes. Analysis of the primary sequence revealed that the two halves of the AQP1 polypeptide are tandem repeats; site directed mutagenesis studies indicate that the repeats may fold into an obversely symmetric structure which resembles an hourglass. Electron crystallography elucidated the tetrameric organization of AQP1, and functional studies suggest that each tetramer contains multiple functionally independent aqueous pores. AQP1 is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in multiple extra renal tissues. AQP2 is expressed only in the principal cells of renal collecting duct where it is the predominant vasopressin (ADH, antidiuretic hormone) regulated water channel. AQP2 is localized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by ADH. Humans with mutations in genes encoding AQP1 and AQP2 exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of renal collecting duct principal cells providing an exit pathway for water; AQP4 is abundant in brain where it may function as the hypothalamic osmoreceptor responsible for secretion of ADH. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and disorders of water balance.
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PMID:The aquaporin family of water channels in kidney. 898 45

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

Nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine in response to vasopressin. The autosomal recessive form of NDI is caused by mutations in the AQP2 gene, encoding the vasopressin-regulated water channel of the kidney collecting duct. This report presents three new mutations in the AQP2 gene that cause NDI, resulting in A147T-, T126M-, or N68S-substituted AQP2 proteins. Expression of the A147T and T126M mutant AQP2 proteins in Xenopus oocytes revealed a relatively small, but significant increase in water permeability, whereas the water permeability of N68S expressing oocytes was not increased. cRNA encoding missense and wild-type AQP2 were equally stable in oocytes. Immunoblots of oocyte lysates showed that only the A147T mutant protein was less stable than wild-type AQP2. The mutant AQP2 proteins showed, in addition to the wild-type 29-kd band, an endoplasmic reticulum-retarded form of AQP2 of approximately 32 kd. Immunoblotting and immunocytochemistry demonstrated only intense labeling of the plasma membranes of oocytes expressing wild-type AQP2. In summary, two mutant AQP2 proteins encoded in NDI are functional water channels. Therefore, the major cause underlying autosomal recessive NDI is the misrouting of AQP2 mutant proteins.
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PMID:New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels. 904 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

During antidiuresis, increases in vasopressin (AVP)-elicited osmotic water permeability in the terminal inner medullary collecting duct (tIMCD) raise luminal calcium concentrations to levels (> or = 5 mM) above those associated with the formation of calcium-containing precipitates in the urine. Calcium/polycation receptor proteins (CaRs) enable cells in the parathyroid gland and kidney thick ascending limb of Henle to sense and respond to alterations in serum calcium. We now report the presence of an apical CaR in rat kidney tIMCD that specifically reduces AVP-elicited osmotic water permeability when luminal calcium rises. Purified tIMCD apical membrane endosomes contain both the AVP-elicited water channel, aquaporin 2, and a CaR. In addition, aquaporin 2-containing endosomes also possess stimulatory (G(alpha q)/G(alpha 11) and inhibitory (G(alpha i1, 2, and 3)) GTP binding proteins reported previously to interact with CaRs as well as two specific isoforms (delta and zeta) of protein kinase C. Immunocytochemistry using anti-CaR antiserum reveals the presence of CaR protein in both rat and human collecting ducts. Together, these data provide support for a unique tIMCD apical membrane signaling mechanism linking calcium and water metabolism. Abnormalities in this mechanism could potentially play a role in the pathogenesis of renal stone formation.
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PMID:Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. 907 50

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


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