UNIPROT:P41181 - FACTA Search

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Query: UNIPROT:P41181 (collecting duct)
5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.
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PMID:Contribution of vasopressin to progression of chronic renal failure: study in Brattleboro rats. 1049 67

The reduction of urinary volume after the use of thiazide in the treatment of diabetes insipidus (DI) is known as the "paradoxical effect." Since enhanced proximal solute and water reabsorption only partially account for the reduction in urinary volume, an additional diuretic effect on nephron terminal segments was postulated. Thus the aim of our work was to investigate the effect of hydrochlorothiazide (HCTZ) on water transport in the inner medullary collecting duct (IMCD) of normal and Brattleboro rats. Osmotic water permeability (P(f)) and diffusional water permeability (P(dw)) were studied at 37 degrees C and pH 7.4 by the in vitro microperfusion technique. In the absence of antidiuretic hormone (ADH), HCTZ (10(-6) M) added to the perfused fluid enhanced P(f) from 6.36 +/- 0. 56 to 19.08 +/- 1.70 micro(m)/s (P < 0.01) and P(dw) from 38.01 +/- 4.52 to 52.26 +/- 4.38 x10(-5) cm/s (P < 0.01) in normal rats and also stimulated P(f) in Brattleboro rats from 3.53 +/- 1.41 to 11.16 +/- 1.13 micro(m)/s (P < 0.01). Prostaglandin E(2) (PGE(2)) (10(-5) M) added to the bath fluid inhibited HCTZ-stimulated P(f) (in micro(m)/s) as follows: control, 16.93 +/- 2.64; HCTZ, 29.65 +/- 5.67; HCTZ+PGE(2), 10.46 +/- 1.84 (P < 0.01); recovery, 16.77 +/- 4.07. These data indicate that thiazides enhance water absorption in IMCD from normal rats (in the absence of ADH) and from Brattleboro rats and that the HCTZ-stimulated P(f) was partially blocked by PGE(2). Thus we may conclude that the effect of thiazide in the treatment of DI occurs not only in the Na(+)-Cl(-) cotransport in the distal tubule but also in the IMCD.
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PMID:Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats. 1056 39

The central and peripheral mechanisms regulate body water balance near an ideal set point. Osmosensitive neurons in the organum vasculosum lamina terminalis (OVLT) in the anterior hypothalamus play a key role in regulating vasopressin release and drinking behaviour. Patients with OVLT lesions are known to have osmostat fluctuations. Although the brain water channel is suggested to participate in osmoreception, the precise molecular mechanisms of osmoreception and thirst appreciation remain to be clarified. Vasopressin gene mutation is responsible for hereditary central diabetes insipidus. Mutant vasopressin precursors have been reported to impair the secretion of wild-type proteins or cause cellular toxicity. Despite the intact production and secretion of vasopressin, the kidney is unable to concentrate urine in nephrogenic diabetes insipidus (NDI). Most congenital NDI patients have mutations in the G protein-coupled vasopressin V2 receptor gene. V2 receptor mutants are shown not to reach the plasma membrane, not to bind AVP, and not to trigger an intracellular cyclic adenosine-monophosphate signal. Congenital NDI with an autosomal recessive inheritance has mutations of Aquaporin-2 gene, a vasopressin-sensitive water channel in the renal inner medullary collecting duct (IMCD). Aquaporin-2 mutant proteins cannot be expressed at the luminal membrane. The corticopapillary osmotic gradient is necessary for renal sensitivity to vasopressin. The vasopressin-regulated urea transporter in IMCD and the chloride channel (CLC-K1) in the ascending loop of the Henle contribute to the formation of the osmotic gradient. NDI has been shown in mice lacking the CLC-K1. The pathophysiological significance of urea transporter and CLC-K1 has yet to be demonstrated in patients with NDI.
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PMID:[Water metabolism and its disturbances]. 1063 21

Aquaporin-2 (AQP-2) is an arginine vasopressin (AVP)-regulated water channel in renal collecting duct cells. Approximately 3 % of AQP-2 in collecting duct cells is excreted into urine. Urinary excretion of AQP-2 varies widely in different physiological conditions, and it has a positive correlation with plasma AVP levels. Urinary excretion of AQP-2 was significantly increased by the single injection of AVP in patients with central diabetes insipidus. The urinary excretion of AQP-2 was one-eighth over in patients with central diabetes insipidus and three times greater in patients with impaired water excretion than that in normal subjects. In a hypertonic saline test, the urinary excretion of AQP-2 promptly increased 6-12-fold in normal subjects, but remained low in patients with central diabetes insipidus. In addition, exaggerated urinary excretion of AQP-2 persisted after an acute water load in patients with impaired water excretion. These results indicate that urinary excretion of AQP-2 is a potent marker for the diagnosis of water metabolism disorders dependent on AVP.
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PMID:Urinary excretion of aquaporin-2 in pathological states of water metabolism. 1076 99

The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have shown that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. A series of studies have underscored crucial roles of aquaporins for regulation of renal water metabolism and hence body water balance. Moreover it has become clear that dysregulation of aquaporins, and especially AQP2 is critically involved in many water balance disorders. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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PMID:Physiology and pathophysiology of renal aquaporins. 1132 Apr 86

The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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PMID:Aquaporins in the kidney: from molecules to medicine. 1177 13

Alterations in water metabolism are present in conditions such as diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, cardiac failure, cirrhosis, and pregnancy. Recent advances in molecular biology have enhanced our understanding of disordered water metabolism in these conditions. This review examines the roles of central vasopressin synthesis and release and collecting duct vasopressin V2 receptor and aquaporin-2 water channel regulation in water-losing and water-retaining states.
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PMID:Water-losing and water-retaining states: role of water channels and vasopressin receptor antagonists. 1197 94

In diabetes insipidus, the amount of water ingested and the quantity and concentration of urine produced needs to be carefully regulated if fluid volume and osmolality are to be maintained within the normal range. One of the principal mechanisms controlling urine output is vasopressin which is released from the posterior pituitary gland and enhances water reabsorption from the renal collecting duct. In diabetes insipidus, the excessive production of dilute urine, and the causes of this clinical picture can be divided into three main groups: the first is primary polydipsia where the amount of fluid ingested is inappropriately large; the second group is cranial diabetes insipidus where the production of vasopressin is abnormally low; and, the third group is nephrogenic diabetes insipidus where the kidney response to vasopressin is impaired. The history and examination may suggest an underlying explanation for diabetes insipidus but a range of baseline and more extensive investigations may be required before a diagnosis can be reached. These investigations are not without risk, and the results need to be interpreted carefully because children do not always segregate neatly into a particular diagnostic category on the basis of one test alone. Children with cranial diabetes insipidus typically respond to arginine vasopressin or its manufactured analogue, desmopressin, with an increase in urine osmolality and an associated reduction in urine output. Such children usually require neuroimaging to look for evidence of evolving CNS pathology, such as an intracranial tumour. Vasopressin "replacement" with desmopressin is the treatment of choice in patients with cranial diabetes insipidus although extreme caution is required when treating babies or small children because of the danger of fluid overload. Abnormal production of other pituitary hormones in children with CNS disease can also influence fluid balance. Nephrogenic diabetes insipidus can be due to abnormal electrolyte concentrations, therefore these should be measured as part of the initial assessment. In a small number of children the defect is a primary abnormality of the vasopressin receptor or one of the water channel proteins (aquaporins) involved in water transport. The treatment of these patients is difficult and typically involves therapy with a diuretic such as chlorothiazide, as well as indomethacin. These agents enhance urine osmolality by their effect on circulating volume and renal solute and water handling. The fluid intake of most young children with primary polydipsia can be safely reduced to a more appropriate level.
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PMID:Diabetes insipidus in children: pathophysiology, diagnosis and management. 1243 Nov 31

Aquaporins (AQP) are integral membrane proteins that serve as channels in the transfer of water, and in some cases, small solutes across the membrane. They are conserved in bacteria, plants, and animals. Structural analyses of the molecules have revealed the presence of a pore in the center of each aquaporin molecule. In mammalian cells, more than 10 isoforms (AQP0-AQP10) have been identified so far. They are differentially expressed in many types of cells and tissues in the body. AQP0 is abundant in the lens. AQP1 is found in the blood vessels, kidney proximal tubules, eye, and ear. AQP2 is expressed in the kidney collecting ducts, where it shuttles between the intracellular storage sites and the plasma membrane under the control of antidiuretic hormone (ADH). Mutations of AQP2 result in diabetes insipidus. AQP3 is present in the kidney collecting ducts, epidermis, urinary, respiratory, and digestive tracts. AQP3 in organs other than the kidney may be involved in the supply of water to them. AQP4 is present in the brain astrocytes, eye, ear, skeletal muscle, stomach parietal cells, and kidney collecting ducts. AQP5 is in the secretory cells such as salivary, lacrimal, and sweat glands. AQP5 is also expressed in the ear and eye. AQP6 is localized intracellular vesicles in the kidney collecting duct cells. AQP7 is expressed in the adipocytes, testis, and kidney. AQP8 is expressed in the kidney, testis, and liver. AQP9 is present in the liver and leukocytes. AQP10 is expressed in the intestine. The diverse and characteristic distribution of aquaporins in the body suggests their important and specific roles in each organ.
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PMID:Aquaporins: water channel proteins of the cell membrane. 1524 1

Polyuria and polydipsia (PUPD) occur frequently in dogs and may be caused by a variety of endocrine, metabolic, and renal disturbances. The studies described in this PhD Thesis, which was defended in January 2004 in Utrecht, investigated the role of the antidiuretic hormone vasopressin (VP) in the pathogenesis of different forms of canine polyuria. Experiments in healthy dogs demonstrated that the ranges of urine specific gravity and urine osmolality are much larger than previously thought. A water deprivation test is not required in all polyuric dogs, because serial measurements of urine osmolality may already lead to the diagnosis of primary polydipsia, in some cases. In dogs with primary polydipsia a wide variation in VP responses to hypertonic stimulation can be found, including a hyperresponse, a hyporesponse, and a non-linear response. The significance of the VP response to hypertonic saline infusion as the 'gold standard' for a diagnosis of canine polyuria is discussed. In the dog, VP is secreted in a pulsatile fashion with a wide variation in the number of VP pulses, VP pulse duration, and VP pulse amplitude and height. The occurrence of spontaneous VP pulses may severely hamper the interpretation of the curve describing the relationship between plasma osmolality and plasma VP concentration during osmotic stimulation. A radioimmunoassay to measure the VP-dependent water channel aquaporin-2 (AQP2) in urine was developed in dogs. In healthy dogs, urinary AQP2 excretion closely reflects changes in collecting duct exposure to VP. Measurement of urinary AQP2 excretion in polyuric dogs may be helpful to distinguish between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia.
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PMID:[The role of vasopressin in dogs with polyuria]. 1562 96

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