Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been cloned and shown to form a sub-family within the large superfamily of G-protein-linked receptors. Renal V2 receptors mediate vasopressin-induced water reabsorption via induction of intracellular cAMP production in collecting duct cells. Most remaining actions of vasopressin on blood vessel constriction, liver glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain brain functions are mediated via v1a-type receptors that are coupled to a Gq/11 protein. V1 receptor activation leads to stimulation of phospholipases C, D and A2 and an increase in intracellular calcium. Vasopressin stimulates pituitary corticotrophin release via a third vasopressin receptor type (V1b) which is present on corticotrophs. Oxytocin induces myometrial contraction, endometrial prostaglandin F2 alpha production, mammary gland milk ejection, renal natriuresis and specific sexual, affiliative and maternal behaviours via oxytocin receptors which are also coupled to a Gq/11 protein. Although only one oxytocin receptor type has been cloned so far, recent binding studies indicate that uterine endometrial oxytocin receptors may constitute a distinct receptor subtype. In contrast to most other membrane receptors, the expression of oxytocin receptors undergoes very rapid and physiologically relevant up-and-down-regulation. A > 100-fold up-regulation of uterine oxytocin receptors occurs during gestation and may represent the trigger for parturition. Indeed, oxytocin receptor antagonists are able to counteract preterm labour and may soon be available for clinical use. The presence of oxytocin receptors on breast cancer cells and the growth-inhibitory effects of OT suggest a potential use of oxytocin analogues for breast cancer treatment. Whereas no mutations of the oxytocin or V1a or V1b receptors have been found, over 60 different genetic mutations of the (renal) V2 receptor have been described which represent the cause for congenital nephrogenic diabetes insipidus.
 ...
PMID:Vasopressin and oxytocin receptors. 873 52

Vasopressin-dependent membrane insertion of aquaporin-2 (AQP-2) in collecting duct principal cells has been demonstrated in vivo and in vitro. However, the hypothesis that the AQP-2 molecule recycles between intracellular vesicles and the plasma membrane in response to hormonal stimulation and withdrawal remains to be demonstrated directly. In the present study, we examined AQP-2 recycling between intracellular vesicles and the plasma membrane in the absence of de novo protein synthesis using LLC-PK1 cells transfected with an AQP-2-c-myc construct. Cells were treated with cycloheximide for 30 min prior to vasopressin stimulation, and all subsequent treatments were performed in the continued presence of cycloheximide. Complete inhibition of AQP-2 biosynthesis by cycloheximide was verified by immuno-precipitation. Immunofluorescence revealed that AQP-2 was located on intracellular vesicles in nonstimulated cells but was relocated to the plasma membrane after vasopressin treatment, even in the presence of cycloheximide. After vasopressin washout, AQP-2 was retrieved to intracellular vesicles and was relocated to the plasma membrane after restimulation with forskolin. Subsequent forskolin washout resulted in AQP-2 endocytosis, and a second stimulation with forskolin resulted in relocation to the plasma membrane. These data, obtained in the absence of de novo protein synthesis, clearly indicate that AQP-2 can be recycled multiple times between intracellular vesicles and the plasma membrane.
 ...
PMID:Direct demonstration of aquaporin-2 water channel recycling in stably transfected LLC-PK1 epithelial cells. 878 Feb 59

Aquaporin-2 (AQP-2) has been shown to be a vasopressin-sensitive water channel in collecting duct (CD) cells of the kidney. To prove the role of the vasopressin V2 receptor (V2R) in the regulation of intracellular AQP-2 shuttling, we examined the acute effects of vasopressin and V2R antagonist on the distribution of AQP-2 in the cells. Normal Wistar rats were given continuous infusions of vasopressin, vasopressin V2R antagonist (OPC31260), or both. The kidneys were then processed for immunofluorescent studies with an affinity-purified specific antibody to AQP-2. One hour after the infusion of the V2R antagonist, AQP-2 staining was diffusely distributed in the CD cells from the cortex to the inner medulla. This tendency was not changed by the concomitant infusion with vasopressin. Vasopressin infusion without antagonist, however, induced intensified AQP-2 staining of the apical membrane in the CD cells. The ratio of the fluorescence intensity of the apical to subapical region was determined by confocal laser microscopy. In the inner medulla, this ratio was significantly increased in the vasopressin treatment group (2.26 +/- 0.76) as compared to the V2R antagonist group (1.03 +/- 0.34) and the combined treatment group (0.84 +/- 0.43). The increase in the ratio was also demonstrated in the cortex and the outer medulla in the vasopressin-treated group. In addition, Northern blotting studies clearly revealed that mRNA of AQP-2 in the vasopressin-treated group was increased when compared to the combined treatment animals. Our present results reveal that localization and gene expressions of AQP-2 are acutely regulated via vasopressin V2R.
 ...
PMID:Role of vasopressin V2 receptor in acute regulation of aquaporin-2. 881 15

Vasopressin V2 receptors, expressed from an x-chromosomal gene, are involved in antidiuresis, but also in release of coagulation factor VIII and von Willebrand factor (vWF). The present study describes autosomal recessive nephrogenic diabetes insipidus (NDI) in a large cluster of patients in Israel's Lower-Galilee. Evidence for an intact V2 receptor was concluded by their normal increase in factor VIII and vWF after desmopressin infusion. Thus, in these patients a defect in the pathway beyond the V2 receptor was suspected. The recent cloning of the human Aquaporin-2 gene enabled us to test this gene as a candidate for such a postreceptor defect. Direct sequencing of the Aquaporin-2 gene revealed a G298T substitution causing a Gly100Stop nonsense mutation in the third transmembrane region. Because this putative disease-causing mutation was identified in index patients of different families, we suggest that all patients are descendants of a common ancestor. Thus, this new entity is characterized by an autosomal recessive NDI. The differential response of clotting factors and urine osmolality to desmopressin may provide a simple tool for clinical diagnosis of a V2-postreceptor defect. The early stop-codon of Aquaporin-2 results in complete resistance to vasopressin antidiuretic effect.
 ...
PMID:Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2 mutation. 902 77

Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.
 ...
PMID:Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. 914 44

Aquaporins are proteins that mediate transmembrane water transport in a variety of tissues including the kidney. Vasopressin plays an important role in regulation of water metabolism, and under normal conditions the kidney collecting duct is extremely sensitive to vasopressin. Vasopressin stimulates the synthesis of aquaporin 2 (AQP2) in kidney collecting duct principal cells. Studies in Brattle Boro rats which are vasopressin deficient, revealed low levels of AQP2 in association with extreme polyuria. After vasopressin treatment for 5 days AQP2 levels increased threefold. Using rat models with nephrogenic diabetes insipidus (NDI) we have demonstrated that AQP2 expression is down regulated in association with polyuria, suggesting that reduced levels of AQP2 may be a general factor in acquired forms of NDI from a variety of reasons. The polyuria and urinary concentrating defects associated with an abnormal nightly-increase in AVP in patients with nocturnal enuresis may partly be due to a lack of vasopressin-mediated AQP2 expression since treatment with desmopressin in these patients have normalised their nocturnal urine production.
 ...
PMID:Do aquaporins have a role in nocturnal enuresis? 916 2

Antidiuretic hormone leads to an increase in the permeability for water and urea in the inner medullary collecting duct. Hence, urea may not be an "effective" osmole in the inner medulla during maximal renal water conservation. Accordingly, the purpose of this study was to evaluate whether differences in the rate of urea excretion would influence maximum renal water conservation in humans. In water-deprived rats, the concentration of urea and total osmolality were somewhat higher in the urine exiting the inner medullary collecting duct than in interstitial fluid obtained from the entire papillary tip. Nevertheless, the "nonurea" (total osmolality minus urea in millimolar terms) osmolality was virtually identical in both locations. Chronically fasted human subjects that were water-deprived for 16 h had a lower rate of urea excretion (71 +/- 7 versus 225 +/- 14 mumol/min) and a somewhat lower urine osmolality (745 +/- 53 versus 918 +/- 20 mosmol/kg H2O). Nevertheless, they had identical urine flow rates (0.5 +/- 0.01 and 0.5 +/- 0.02 ml/min, respectively), and their nonurea osmolality also was similar (587 +/- 25 and 475 +/- 14 mosmol/kg H2O, respectively) to the water-deprived normal subjects. The composition of their urine differed in that the principal nonurea osmoles became NH4+ and beta-hydroxybutyrate rather than Na and C1. During water deprivation in normal subjects, the ingestion of urea caused a twofold rise in urine flow rate, a fall in the nonurea osmolality, and a rise in the rate of excretion of nonurea osmoles. The nonurea osmolality of the urine, and presumably the medullary interstitial fluid as well, was inversely related to the urea excretion rate. In chronic fasting, the nature, but not the quantity, of nonurea osmoles changed. The similar minimum urine volume was predictable from an analysis based on nonurea osmole considerations.
 ...
PMID:Minimum urine flow rate during water deprivation: importance of the nonurea versus total osmolality in the inner medulla. 918 53

Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renal collecting duct. The aquaporin-2 water channel has been demonstrated to be the target for this action of vasopressin. Recent studies have demonstrated that vasopressin, acting through cyclic AMP, triggers fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principal cells. The vesicle-targeting proteins synaptobrevin-2 and syntaxin-4 are proposed to play roles in this process.
 ...
PMID:Regulation of aquaporin-2 water channel trafficking by vasopressin. 926 Oct 56

Vasopressin is the key regulator of water homeostasis in vertebrates. Central to its antidiuretic action in mammals is the redistribution of the water channel aquaporin 2 (AQP2) from intracellular vesicles to the apical membrane of kidney epithelial cells, an event initiated by an increase in cAMP and activation of protein kinase A. The subsequent steps of the signaling cascade are not known. To identify proteins involved in the AQP2 shuttle we exploited a recently developed cell line (CD8) derived from the rabbit cortical collecting duct and stably transfected with rat AQP2 cDNA. Treatment of CD8 cells with pertussis toxin (PTX) inhibited both the vasopressin-induced increase in water permeability and the redistribution of AQP2 from an intracellular compartment to the apical membrane. ADP-ribosylation studies revealed the presence of at least two major PTX substrates. Correspondingly, two alpha subunits of PTX-sensitive G proteins, Galphai2 and Galphai3, were identified by Western blotting. Introduction of a synthetic peptide corresponding to the C terminus of the Gi3 alpha subunit into permeabilized CD8 cells efficiently inhibited the cAMP-induced AQP2 translocation; a peptide corresponding to the alpha subunits of Gi1/2 was much less potent. Thus a member of the Gi family, most likely Gi3, is involved in the cAMP-triggered targeting of AQP2-bearing vesicles to the apical membrane of kidney epithelial cells.
 ...
PMID:A heterotrimeric G protein of the Gi family is required for cAMP-triggered trafficking of aquaporin 2 in kidney epithelial cells. 971 91

Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.
 ...
PMID:Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy. 975 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>