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)

Regulation of total body water balance in amphibians by antidiuretic hormone (ADH) contributed to their successful colonization of terrestrial habitats approximately 200-300 million years ago. In the mammalian kidney, ADH modulates epithelial cell apical membrane water permeability (Pf) by fusion and retrieval of cytoplasmic vesicles containing water channel proteins called aquaporins (AQPs). To determine the role of AQPs in ADH-elicited Pf in amphibians, we have identified and characterized a unique AQP from Bufo marinus called AQP toad bladder (AQP-TB). AQP-TB possesses many structural features common to other AQPs, AQP-TB is expressed abundantly in ADH-responsive tissues, including toad urinary bladder and skin as well as lung, skeletal muscle, kidney, and brain. In a manner identical to that reported for the mammalian ADH-elicited water channel AQP2, AQP-TB expression is increased significantly by intervals of dehydration or chronic ADH stimulation. However, expression of AQP-TB protein in Xenopus laevis oocytes does not significantly increase oocyte Pf. The lack of expression of functional AQP-TB water channels in oocytes may result from intracellular sequestration of AQP-TB due to the presence of a YXRF sequence motif present in its carboxyterminal domain.
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PMID:Cloning of an aquaporin homologue present in water channel containing endosomes of toad urinary bladder. 877 65

Hereditary nephrogenic diabetes insipidus (NDI) is caused by mutations in either the X-chromosomal gene encoding the vasopressin V2-receptor or in the autosomal gene encoding aquaporin-2. Expressed in Xenopus oocytes, the AQP2 gene mutations found in NDl have been shown to reduce the stability of the encoded protein. This study investigated the in vivo stability of mutant and wild-type aquaporin-2 proteins by measuring their excretion in urine of NDl patients and healthy individuals. On immunoblots, the urine samples from healthy volunteers revealed clear aquaporin-1 and aquaporin-2 signals in antidiuretic but not diuretic states. In the urine of a female patient, whose NDl is explained by low expression of the wild-type V2-receptor gene, aquaporin-2 excretion was high and comparable with that in a healthy individual during antidiuresis. In the urine of a male patient with a non-sense mutation in the V2-receptor gene, a weak aquaporin-2 signal was detected. In NDl patients with mutations in the aquaporin-2 gene, aquaporin-2 could not be detected in urine, suggesting a low stability of mutant aquaporin-2 proteins. In four out of seven NDl patients, aquaporin-1 excretion was relatively high, which suggests a compensatory increase in proximal reabsorption in NDl.
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PMID:Urinary content of aquaporin 1 and 2 in nephrogenic diabetes insipidus. 879 91

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

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

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

Transepithelial water permeability was measured in LLC-PK1 cells stably transfected with aquaporins (AQPs): AQP1, AQP2, and a chimera of AQP1 and AQP2 containing 41 amino acids of the C-terminus of AQP2. Transepithelial water fluxes (Jw) were not previously reported in cells transfected with aquaporins. Jw were now recorded each minute using a specially developed experimental device. A significant increase in Posm after forskolin (FK) plus vasopressin (VP) was found in AQP2 transfected cells (39.9 +/- 8.2 vs. 12.5 +/- 3.3 cm.sec-1.10(-3)), but not in cells transfected with AQP1 (15.3 +/- 3.6 vs. 13.4 +/- 3.6 cm.sec-1.10(-3)). In the case of the AQP1/2 cells (chimera) the FK plus VP induced Posm was smaller than in AQP2 cells but significantly higher than in mock cells at rest (18.1 +/- 4.8 vs. 6.7 +/- 1.0 cm.sec-1.10(-3)). The increases in Posm values were not paralleled by increases in 14C-Mannitol permeability. HgCl2 inhibited the hydrosmotic response to FK plus VP in AQP2 transfected epithelia. Results were comparable to those observed, in parallel experiments, in a native ADH-sensitive water channel containing epithelial barrier (the toad urinary bladder). Electron microscopy showed confluent LLC-PK1 cells with microvilli at the mucosal border. The presence of spherical or elongated intracellular vacuoles was observed in AQP2 transfected cells, specially after FK plus VP stimulus and under an osmotic gradient. These results demonstrate regulated transepithelial water permeability in epithelial cells transfected with AQP2.
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PMID:Reconstitution of a regulated transepithelial water pathway in cells transfected with AQP2 and an AQP1/AQP2 hybrid containing the AQP2-C terminus. 943 70

Water channel aquaporin-1 (AQP1) is strongly expressed in kidney in proximal tubule and descending limb of Henle epithelia and in vasa recta endothelia. The grossly normal phenotype in human subjects deficient in AQP1 (Colton null blood group) and in AQP4 knockout mice has suggested that aquaporins (other than the vasopressin-regulated water channel AQP2) may not be important in mammalian physiology. We have generated transgenic mice lacking detectable AQP1 by targeted gene disruption. In kidney proximal tubule membrane vesicles from knockout mice, osmotic water permeability was reduced 8-fold compared with vesicles from wild-type mice. Although the knockout mice were grossly normal in terms of survival, physical appearance, and organ morphology, they became severely dehydrated and lethargic after water deprivation for 36 h. Body weight decreased by 35 +/- 2%, serum osmolality increased to >500 mOsm, and urinary osmolality (657 +/- 59 mOsm) did not change from that before water deprivation. In contrast, wild-type and heterozygous mice remained active after water deprivation, body weight decreased by 20-22%, serum osmolality remained normal (310-330 mOsm), and urine osmolality rose to >2500 mOsm. Urine [Na+] in water-deprived knockout mice was <10 mM, and urine osmolality was not increased by the V2 agonist DDAVP. The results suggest that AQP1 knockout mice are unable to create a hypertonic medullary interstitium by countercurrent multiplication. AQP1 is thus required for the formation of a concentrated urine by the kidney.
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PMID:Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. 946 75

1. The mechanism underlying the antidiuretic effect of thiazide diuretics in diabetes insipidus (DI) is unknown. This study addressed two specific questions: is the reduction in urine flow rate (V) related to a decrease in the delivery of fluid from the pars recta of the proximal tubules ('distal delivery'), and are there any changes in the expression and/or intracellular distribution of vasopressin stimulated water channels (AQP2) in the collecting ducts, during chronic thiazide-induced antidiuresis? 2. Nine Brattleboro rats with vasopressin-deficient DI were treated for 5 days with bendroflumethiazide (BFTZ), 9 mg kg(-1) day(-1) orally, and 9 Brattleboro rats were left untreated. BFTZ-treated DI rats showed a fall in V from approximately 200 to approximately 75 ml day(-1) and an increase in urine osmolality from approximately 130 to approximately 400 mosmol kg(-1). 3. BFTZ-induced antidiuresis was associated with a persistent loss of sodium, but not of potassium. After 5 days of treatment, clearance studies in conscious rats showed a tendency towards decreases in effective renal plasma flow (-7%), GFR (-12%) and lithium clearance (C(Li); used as marker for distal delivery) (-25%), compared with untreated controls, but none of these changes were statistically significant. There was no apparent relationship between C(Li) and V in BFTZ-treated or untreated DI rats. 4. BFTZ treatment did not change the expression of AQP2 in homogenates of cortex, outer or inner medulla from DI rats, or from normal Long Evans rats. Light and electron microscopic immunocytochemistry revealed no changes in intracellular distribution of AQP2 in principal cells from inner medullary collecting ducts of BFTZ-treated DI rats. 5. We concluded, (i) that although the antidiuretic effect of BFTZ in rats with DI is associated with a net loss of Na, the decrease in V shows no association with changes in distal delivery, as estimated by C(Li). (ii) Antidiuretic treatment with BFTZ does not alter the expression of subcellular distribution of AQP2 water channels in the collecting ducts. The mechanism underlying the chronic antidiuresis caused by thiazide diuretics in DI remains elusive.
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PMID:Mechanism of antidiuresis caused by bendroflumethiazide in conscious rats with diabetes insipidus. 951 94

Disorders of serum sodium are both the most common and probably most the poorly understood electrolyte disorders in clinical medicine. In the past few years increased knowledge about the non-osmotic release of vasopressin and the cloning of vasopressin receptors and of vasopressin-regulated water channels (AQP2) has enhanced our understanding of these disorders. Also controversies surrounding the treatment of hyponatraemic patients have led to well-accepted therapeutic guidelines.
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PMID:Sodium. 979 16

Aquaporins (AQPs) are a family of functionally important water channel proteins that are of special cell biological interest because of their diverse intracellular targeting and trafficking properties. AQPs have been found in many different cells and tissues. This short review summarizes recent work that addresses the regulation of AQP2 trafficking in response to vasopressin.
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PMID:Cellular mechanisms of aquaporin trafficking. 972 3


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