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)

Vesicle targeting proteins ("SNAREs") have been proposed to direct vasopressin-induced trafficking of aquaporin-2 water channels in kidney collecting ducts. A newly identified SNARE protein, SNAP-23, is proposed to mediate vesicle targeting to the plasma membrane in diverse tissues. The current studies were done to determine whether SNAP-23 is expressed in collecting ducts with an intracellular distribution compatible with a role in aquaporin-2 trafficking. RT-PCR demonstrated SNAP-23 mRNA in microdissected collecting ducts and other tubular segments including the proximal tubule and thick ascending limb. Immunoblotting using a polyclonal antibody raised against a COOH-terminal peptide revealed a solitary band at an apparent molecular mass of 30 kDa in renal medullary membrane fractions and inner medullary collecting duct suspensions. Differential centrifugation revealed that SNAP-23 is present in membrane fractions including the low-density fraction enriched in intracellular vesicles. Immunocytochemistry revealed SNAP-23 labeling at both the apex and the cytoplasm of collecting duct principal cells. Immunoblotting of intracellular vesicles immunoisolated using an aquaporin-2 antibody revealed the presence of both SNAP-23 and synaptobrevin-2 (VAMP-2) in aquaporin-2-bearing vesicles. We conclude that SNAP-23 is strongly expressed in collecting duct principal cells, consistent with a role in vasopressin-regulated trafficking of aquaporin-2. However, localization of SNAP-23 in both intracytoplasmic vesicles and plasma membranes suggests a function different from that originally proposed for SNAP-25 in synaptic vesicle targeting.
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PMID:SNAP-23 in rat kidney: colocalization with aquaporin-2 in collecting duct vesicles. 981 32

Several aquaporin-type water channels are expressed in mammalian kidney and lung: AQP1 in lung microvessels and kidney proximal tubule, thin descending limb of Henle, and vasa recta; AQP2 in apical membrane of collecting duct epithelium; AQP3 and AQP4 in basolateral membranes of airway and collecting duct epithelium; and AQP5 in alveolar epithelium. Novel quantitative fluorescence methods demonstrated very high water permeabilities of the alveolar epithelial and endothelial barriers, and moderately high water permeability across distal airways. In the kidney, water permeability is high in proximal tubule and thin descending limb of Henle, and regulated by vasopressin in collecting duct. The author's laboratory has studied the role of aquaporins in organ physiology using transgenic knockout mice lacking specific aquaporins. AQP1 null mice are mildly growth-retarded, manifest a severe urinary concentrating defect, and have reduced water permeability between airspace and capillary compartments. AQP4 null mice appear normal grossly except for a mild defect in maximum urinary concentrating ability. AQP2-deficient humans have hereditary non-X-linked nephrogenic diabetes insipidus (NDI). In transfected mammalian cells, many NDI-causing AQP2 mutants are retained in the endoplasmic reticulum. The author's laboratory has found that "chemical chaperones," that is, small compounds that promote protein folding in vitro, are able to correct defective AQP2 trafficking in cell culture models. The transgenic mouse and mammalian cell models are thus beginning to provide clues about the role of aquaporins in normal physiology and disease.
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PMID:Role of aquaporin water channels in kidney and lung. 982 13

The discovery of water channels (aquaporins) was a breakthrough in research on water transport. Aquaporins are a family of intrinsic membrane proteins that function as water-selective channels (except aquaporin-3 and aquaporin-7, which are permeable to urea and glycerol as well) in the plasma membranes of many cells. Aquaporin-0 (MIP26) functions to maintain fluid balance in the lens. Aquaporin-1 is involved in water reabsorption in the kidney's proximal tubules and the thin descending Henle's loop, aqueous humor formation in eye, cerebrospinal fluid formation in brain, and airway hydration in lung. Aquaporin-2 is the only water channel that is activated by vasopressin to enhance water reabsorption in the kidney collecting duct. Aquaporin-3 also contributes to water reabsorption in the kidney collecting duct but is unresponsive to vasopressin. It also appears that aquaporin-3 may contribute to cornea transparency. Aquaporin-4 is involved in cerebrospinal fluid transport in brain, water transport in the kidney collecting duct, aqueous humor transport in the eye, and airway hydration in the lung. Aquaporin-5 apparently is coupled to fluid secretion in exocrine tissues. Although the exact function of aquaporin-6 is not known due to its uncertain localization, its restricted presence in the kidney may suggest a potential role in water transport. Aquaporin-7 appears to play a role in the cryopreservation of the sperm whereas aquaporin-8 is responsible for the secretion of pancreatic juice. The major focus of this review is a discussion of aquaporins in renal epithelia, and particularly the mechanisms associated with vasopressin-mediated water transport involving aquaporin-2 and the signal transduction pathways linked to vasopressin action.
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PMID:Aquaporins (water channels): role in vasopressin-activated water transport. 982 41

Primary cells of renal proximal tubule epithelium (S1 segment) of human kidney (HRPTE cells) up-regulate aquaporin-1 (AQP-1) expression in response to hyperosmolarity. NaCl and D(+)-raffinose increased (2-2.5 fold) AQP-1 expression when medium osmolarity was 400 and 500 mOsm/kg.H2O. Urea did not have this effect. Unlike our previous findings with mIMCD-3 cells, vasopressin (10(-8)M) did not affect AQP-1 expression in HRPTE cells in isosmolar or NaCl-enriched hyperosmolar conditions. Furthermore, HRPTE cells increased (3-4 fold) AQP-1 expression when exposed to hyperosmolar Reno-60 and Hypaque-76 (diatrizoates, ionic) contrast agents at 400 and 500 mOsm/kg.H2O. Isosmolar (290 mOsm/kg H2O) Visipaque (iodixanol, non-ionic) at 10% (v/v) concentrations also increased AQP-1 expression, and 25% v/v of Visipaque rendered morphological alterations of HRPTE cells and a 3-fold increase in AQP-1 expression after 24h exposure. Finally, semi-quantitative RT-PCR of HRPTE cells subjected to various isosmolar or hyperosmolar conditions demonstrated up-regulation of AQP-1 mRNA and protein levels. Our results suggest AQP-1 up-regulation in HRPTE cells exposed to environmental stresses such as hyperosmolarity and high doses of isosmolar contrast agents.
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PMID:Aquaporin-1 expression in proximal tubule epithelial cells of human kidney is regulated by hyperosmolarity and contrast agents. 1006 54

The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.
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PMID:Physiology and pathophysiology of renal aquaporins. 1007 16

Several aquaporin-type water channels are expressed in kidney: AQP1 in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2, AQP3, and AQP4 in the collecting duct; AQP6 in the papilla; and AQP7 in the proximal tubule. AQP2 is the vasopressin-regulated water channel that is important in hereditary and acquired diseases affecting urine-concentrating ability. It has been difficult to establish the roles of the other aquaporins in renal physiology because suitable aquaporin inhibitors are not available. One approach to the problem has been to generate and analyze transgenic knockout mice in which individual aquaporins have been selectively deleted by targeted gene disruption. Phenotype analysis of kidney and extrarenal function in knockout mice has been very informative in defining the role of aquaporins in organ physiology and addressing basic questions regarding the route of transepithelial water transport and the mechanism of near iso-osmolar fluid reabsorption. This article describes new renal physiologic insights revealed by phenotype analysis of aquaporin-knockout mice and the prospects for further basic and clinical developments.
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PMID:Lessons on renal physiology from transgenic mice lacking aquaporin water channels. 1023

Within the past decade an entire family of membrane proteins--aquaporins--which function as transmembrane water channels has been identified; they occur throughout the plant, animal, and bacterial kingdoms. Several family members permit glycerol and urea permeability. Most aquaporins are inhibited by mercury. Constitutively expressed aquaporin 1 is the major permeability channel of the proximal tubule, descending thin limb of the loop of Henle, and it is also found in vasa recta. Aquaporin 2 is expressed in the principal cells of the collecting duct where it shuttles between intracellular vesicles and the apical membrane in response to vasopressin. Aquaporin 2 mutations cause nephrogenic diabetes insipidus; increased aquaporin 2 activity is implicated in the pathophysiology of heart failure, cirrhosis, and nephrotic syndrome. Aquaporins 3 and 4 provide basolateral membrane water channels in the collecting duct. These 4 channels and 6 others are also found elsewhere throughout the body. The physiological importance of several of the channels remains unknown. Aquaporin 1 inhibitors might induce useful diuresis, but humans who lack aquaporin 1 have no significant clinical disease. Inhibition of aquaporin 2 activity by vasopressin receptor antagonists may be useful in heart failure, cirrhosis, nephrotic syndrome, and the syndrome of inappropriate antidiuretic hormone (ADH) release.
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PMID:Aquaporin mediated water flux as a target for diuretic development. 1059 41

Dopamine modulates cardiovascular function by actions in the central and peripheral nervous system, by altering the secretion/release of prolactin, pro-opiomelanocortin, vasopressin, aldosterone, and renin, and by directly affecting renal function. Dopamine produced by the renal proximal tubule exerts an autocrine/paracrine action via two classes of dopamine receptors, D1-like (D1 and D5) and D2-like (D2, D3, and D4), that are differentially expressed along the nephron. The autocrine/paracrine function of dopamine, manifested by tubular rather than by haemodynamic mechanisms, becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension. The molecular basis for the dopaminergic dysfunction in hypertension may involve an abnormal post-translational modification of dopamine receptors.
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PMID:D1 dopamine receptor signalling defect in spontaneous hypertension. 1069 8

The heterotrimeric G protein G(s) is required for hormone-stimulated intracellular cAMP generation because it couples hormone receptors to the enzyme adenylyl cyclase. Hormones that activate G(s) in the kidney include parathyroid hormone, glucagon, calcitonin, and vasopressin. Recently, it has been demonstrated that the G(s)alpha gene is imprinted in a tissue-specific manner, leading to preferential expression of G(s)alpha from the maternal allele in some tissues. In the kidney, G(s)alpha is imprinted in the proximal tubule but not in more distal nephron segments, such as the thick ascending limb or collecting duct. This most likely explains why in both humans and mice heterozygous mutations in the maternal allele lead to parathyroid hormone resistance in the proximal tubule whereas mutations in the paternal allele do not. In contrast, heterozygous mutations have little effect on vasopressin action in the collecting ducts. In mice with heterozygous null G(s)alpha mutations (both those with mutations on the maternal or paternal allele), expression of the Na-K-2Cl cotransporter was decreased in the thick ascending limb, suggesting that its expression is regulated by cAMP. The G(s)alpha genes also generate alternative, oppositely imprinted transcripts encoding XLalphas, a G(s)alpha isoform with a long NH(2)-terminal extension, and NESP55, a chromogranin-like neurosecretory protein. The role, if any, of these proteins in renal physiology is unknown.
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PMID:Variable imprinting of the heterotrimeric G protein G(s) alpha-subunit within different segments of the nephron. 1075 Dec 11

This report describes the technique and procedure for perfusing an isolated rabbit kidney with 25 ml heparinized autologous blood in a closed circuit including a pump and an oxygenator. The duration of the operative ischaemia was 5-8 min; the perfusion lasted 2.5 hours. An additional infusion was made to compensate for urinary losses. Renal blood flow increased progressively from 2.01+/-0.1 to 2.65+/-0.22* ml/g kidney weight (kw) per min (*P<0.05). Between the first (P1) and the last (P4) urine collection period the glomerular filtration rate (GFR) fell from 288+/-25 to 217+/-38* microl/g kw per min, urine flow from 5.58+/-1.13 to 4.91+/-0.75 microl/g kw per min, Na+ excretion from 1.07+/-0.19 to 0.63+/-0.12* micromol/g kw per min, K+ excretion from 0.46+/-0.03 to 0.28+/-0.05* micromol/g kw per min, P excretion from 2.5+/-0.2 to 2.0+/-0.5 microg/g kw per min, Ca excretion from 0.4+/-0.1 to 0.12+/-0.05* microg/g kw per min, creatinine excretion from 6.94+/-0.32 to 5.68+/-0.54 microg/g kw per min, glucose excretion from 18.2+/-3.2 to 1.6+/-0.5* microg/g kw per min, the free water clearance (CH2O) from -6.57+/-0.85 to -5.10+/-1.31 microl/g kw per min and urine osmolality from 600+/-52 to 590+/-105 mOsm/kg, urea excretion from 0.75+/-0.16 to 0.95+/-0.13 micromol/g kw per min. Excretion of glucose, P or Ca was observed only above a given plasma threshold value, and no transport maximum was found for glucose or P. Ca reabsorption paralleled the Na reabsorption. The proximal tubule pressure, measured within the 1st h of perfusion, was 12.5+/-1.1 mm Hg. Histological examination at the end of the perfusion showed dilatation of the tubules as in the non-perfused kidneys, and the presence of numerous bacteria. Hypertonic urine (380-1110 mOsm/kg) was observed in the presence of vasopressin, in the latter's absence the urine was hypotonic urine (206-278 mOsm/kg). There was no correlation between renal plasma flow and the GFR. CH2O increased with increasing filtered Na+ load. In conclusion, the blood-perfused, isolated rabbit kidney has a fairly constant functional capacity for approximately 2 h.
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PMID:The functional state of the isolated rabbit kidney perfused with autologous blood. 1095 48


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