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)

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of arginine vasopressin. The disease gene has been assigned to the subtelomeric region of the X chromosome long arm by demonstrating close linkage between NDI and several X-chromosomal DNA markers. The finding of closely linked genetic markers is useful in the diagnosis of NDI. Receptor studies in patients have indicated that NDI might be due to the absence or an abnormality of the adenylate cyclase-bound vasopressin type 2 receptor. This assumption was supported by the discovery of functional vasopressin V2 receptor activity in somatic cell hybrid cell lines that carried at least the distal part of the human X chromosome long arm. Definite evidence for a V2 receptor defect being the cause of NDI was found in a recent study demonstrating point mutations in the V2 receptor gene from affected individuals. Direct mutation analysis is now applicable for accurate carrier detection and early (prenatal) diagnosis.
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PMID:Nephrogenic diabetes insipidus: identification of the genetic defect. 825 44

Hereditary diabetes insipidus can occur in two forms: the first, referred to as central diabetes insipidus, is responsive to vasopressin whereas the second, termed nephrogenic diabetes insipidus, is resistant to treatment. Recent advances in molecular genetics have contributed to elucidate the pathogenesis of these affections. Familial central diabetes insipidus depicts two unsimilar illnesses. The first, characterized by an autosomal dominant transmission, is of delayed onset and worsens progressively all through life. It is related to a heterozygous mutation of the vasopressin precursor gene mainly involving either the sequence encoding for the signal peptide or the one encoding for neurophysin II, the hormone carrier protein. Mutations described to date are responsible for impairment of vasopressin precursor transportation and processing. Therefore mutant protein accumulates in the posterior pituitary which is involved in the persistant bright spot seen on magnetic resonance imaging. The second illness or Wolfram syndrome, autosomal recessive, associates obligatory features: insulin-dependant diabetes, bilateral optic atrophy and more inconstantly: diabetes insipidus, deafness, genito-urinary and neuropsychiatric disturbances. The cause of this syndrome, still unknown, may involve mitochondrial ADN mutations. Familial nephrogenic diabetes insipidus, of neonatal onset, are mainly X-linked and associated to mutations in the V2 receptor gene. About 60 mutations have been described until now. Some rare cases, transmission of which is autosomal recessive, result from homozygous mutations of aquaporin 2 gene, a water channel involved in the water reabsorption in the renal collecting duct. Other mutations will be probably discovered in future. In conclusion, familial diabetes insipidus constitutes an interesting pathogenic model because it may be explained by impairment of vasopressin gene precursor as well as by abnormalities of renal receptor or post receptor mechanisms of the hormone.
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PMID:[Congenital diabetes insipidus. Recent advances in molecular genetics]. 868 70

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

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

Congenital nephrogenic diabetes insipidus is a rare inherited disorder, which is characterized by the inability of the kidney to concentrate urine due to unresponsiveness to antiduretic hormone arginine vasopressin. Defects must be present somewhere in a vasopressin signal transduction pathway in kidney collecting duct. Recent genetic analysis demonstrated that mutations in vasopressin type 2 receptor and water channel aquaporin 2 are responsible for x-linked and autosomal recessive form, respectively. Expression studies of mutant proteins showed that most of the mutations cause severe functional defects, which are compatible with clinical phenotypes. These advances help understanding of molecular mechanism underlying this disease and therefore improve diagnostic and therapeutic approaches.
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PMID:[Vasopressin type 2 receptor mutations in congenital diabetes insipidus]. 970 64

Congenital nephrogenic diabetes insipidus is a rare disorder in which the kidney is insensitive to the antidiuretic hormone, vasopressin. In most cases, a mutation in the vasopressin type 2(V2) receptor gene is the genetic cause of the disease. So far, few cases of congenital nephrogenic diabetes insipidus with hypertension have been reported. We report one male case of congenital nephrogenic diabetes insipidus accompanied by hypertension. The patient was a 24-year-old man who had suffered from polyuria and polydipsia since infancy and had been found to have hypertension at about 16 years. He was admitted to hospital in May 2000 for investigation of polyuria and hypertension with a high plasma level of renin activity of 10.4 ng/ml/hr. On physical examination, the blood pressure was 150/90 mmHg and the daily urinary output was 18.5 l. There was no change in urine volume and urine osmolality after an intramascular injection of vasopressin and water deprivation. The blood pressure and plasma renin activity were increased from 127/73 mmHg to 146/87 mmHg and from 4.9 ng/ml/hr to 6.1 ng/ml/hr, respectively, by a 4-hour dehydration test. He was found to have a C-to-T transition at nucleotide position 675 by sequencing analysis of the V2 receptor gene. After administration of hydrochlorothiazide, both the blood pressure and urine volume were reduced. Consequently, it was suggested that activation of the renin-angiotensin system by dehydration, at least in part, contributed to high blood pressure in this case.
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PMID:[A case of congenital nephrogenic diabetes insipidus accompanied by hypertension]. 1121 16

Nephrogenic diabetes insipidus is caused by an inability of the kidney to concentrate urine despite adequate concentration of vasopressin in blood and is characterized by polyuria, polydipsia, and hyposthenuria in the presence of plasma hyperosmolality. Nephrogenic diabetes insipidus is the result of defects in water homeostasis in the kidney. Nephrogenic diabetes insipidus occurs when the kidneys cannot or do not respond to vasopressin. There are 2 categories of nephrogenic diabetes insipidus. Congenital nephrogenic diabetes insipidus is a rare, inherited, irreversible cause of polyuria and polydipsia in humans that is even rarer in animals. Acquired nephrogenic diabetes insipidus is more common and is often secondary to illness or medication that interferes with the action of vasopressin in the renal tubules. Unlike congenital nephrogenic diabetes insipidus, acquired or secondary nephrogenic diabetes insipidus is often reversible with correction of the associated or causative problem.
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PMID:Water transport in the kidney and nephrogenic diabetes insipidus. 1232 98

Congenital nephrogenic diabetes insipidus (NDI) is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin. Human kindreds with nephrogenic diabetes insipidus have been found to harbor mutations in the vasopressin receptor 2 (Avpr2) gene or the vasopressin-sensitive water channel aquaporin-2 (Aqp2) gene. Development of a treatment is rendered difficult due to the lack of a viable animal model. Through forward genetic screening of ethylnitrosourea-mutagenized mice, we report the identification and characterization of a mouse model of NDI, with an F204V mutation in the Aqp2 gene. Unlike previously attempted murine models of NDI, our mice survive to adulthood and more exactly recapitulate the human disorder. Previous in vitro experiments using renal cell lines suggest recessive Aqp2 mutations result in improper trafficking of the mutant water pore. Using these animals, we have directly proven this hypothesis of improper AQP2 translocation as the molecular defect in nephrogenic diabetes insipidus in the intact organism. Additionally, using a renal cell line we show that the mutated protein, AQP2-F204V, is retained in the endoplasmic reticulum and that this abnormal localization can be rescued by wild-type protein. This novel mouse model allows for further mechanistic studies as well as testing of pharmacological and gene therapies for NDI.
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PMID:Diabetes insipidus in mice with a mutation in aquaporin-2. 1612 Dec 55

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. There are three inheritance patterns of CNDI: the X-linked recessive form associated with vasopressin V2 receptor gene mutations, and the autosomal recessive and dominant forms associated with aquaporin-2 gene (AQP2) mutations. The evaluation for polyuria and polydipsia in a one-month-old Korean girl revealed no response to vasopressin and confirmed the diagnosis of CNDI. Because the child was female without family history of CNDI, her disease was thought to be an autosomal recessive form. We analyzed the AQP2 gene and detected a compound heterozygous missense point mutation: 70Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and 187Arg (CGC) to His (CAC) in exon 3 inherited from her mother. The first mutation is located within the first NPA motif of the AQP2 molecule and the second one right after the second NPA motif. This is the first report to characterize AQP2 mutations in Korean patients with autosomal recessive CNDI, and expands the spectrum of AQP2 mutations by reporting two novel mutation, 70Ala (GCC) to Asp (GAC) and 187Arg (CGC) to His (CAC).
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PMID:Two novel mutations in the aquaporin 2 gene in a girl with congenital nephrogenic diabetes insipidus. 1636 27

Primary nephrogenic diabetes insipidus (NDI) is a genetic, chronic disease characterised by lack of distal renal tubule to antidiuretic hormone. The condition produces polyuria, polydipsia, and consequently, reduced caloric intake and growth failure. There is very scarce information on physical growth of affected children. The objective of the paper is to describe long-term growth of 14 patients from 11 families, studied retrospectively and followed for 3-16 years (median 11.6 years). Diagnosis was made on the basis of clinical and laboratory data and concentration test under pitressin. Patients were treated with indomethacin, thiazides, and amiloride. Weight and standing height was measured periodically at the Laboratory of Anthropometry, following standardised techniques. Information was obtained from clinical notes. The majority of children grew below the third centile of local standards, and many showed improvement of weight, height, and body mass index (BMI) over time. Mean height, weight, and BMI gain during follow-up was 1.72, 1.06, and 1.46 standard deviations (SDs), respectively. Three children who did not adhere to treatment showed growth delay. Height gain during the first 2 years of follow-up was inversely associated with height deficit at diagnosis. Further studies on growth at adolescence and in different mutations are recommended.
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PMID:Long-term growth of children with nephrogenic diabetes insipidus. 1858 16


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