Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Among water channel proteins (aquaporins), aquaporin-collecting duct (AQP-CD) is the vasopressin-regulated water channel. Vasopressin causes cAMP production in the renal collecting duct cells, and this is believed to lead to exocytic insertion of water channel into the apical membrane (shuttle hypothesis). AQP-CD contains a consensus sequence for cAMP-dependent protein kinase, residues at positions 253-256 (Arg-Arg-Gln-Ser). To determine the role of this site, Ser-256 was substituted for Ala, Leu, Thr, Asp, or Glu by site-directed mutagenesis. In Xenopus oocytes injected with wild-type or mutated AQP-CD cRNAs, osmotic water permeability (Pf) was 4.8-7.7 times higher than Pf of water-injected oocytes. Incubation with cAMP plus forskolin or direct cAMP injection into the oocytes increased Pf of wild-type, but not mutated, AQP-CD-expressing oocytes, whereas the amounts of AQP-CD expression were similar in wild and mutated types as identified by Western blot analysis. In vitro phosphorylation studies of AQP-CD proteins expressed in oocyte showed that cAMP-dependent protein kinase phosphorylated wild-type, but not mutated, AQP-CD proteins. Phosphoamino acid analysis revealed that this phosphorylation occurred at the serine residue. Moreover, phosphorylation of AQP-CD protein in intact rat kidney medulla tissues was stimulated by incubation with cAMP. Our data suggest that cAMP stimulates water permeability of AQP-CD by phosphorylation. This process may contribute to the vasopressin-regulated water permeability of collecting duct in addition to the apical insertion of AQP-CD by exocytosis.
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PMID:cAMP-dependent phosphorylation stimulates water permeability of aquaporin-collecting duct water channel protein expressed in Xenopus oocytes. 753 30

Experiments were performed in anesthetized renal-denervated rats to determine the contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the regulation of renal medullary blood flow. Renal medullary interstitial infusion of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1) significantly decreased outer medullary blood flow by 15% and inner medullary blood flow by 35%, as measured with implanted optical fibers for laser-Doppler flowmetry. Medullary interstitial infusion of equimolar doses of arginine vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased inner medullary blood flow by only 17%, a decrease significantly less than that during the infusion of the V1 agonist. These results were confirmed in videomicroscopy experiments on the exposed papilla, which demonstrated that the V1 agonist and AVP decreased descending and ascending vasa recta capillary red blood cell velocity and calculated blood flow, with greater decreases during infusion of the V1 agonist. In further laser-Doppler flowmetry studies, stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D-arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present experiments indicate that vasopressin V1 receptor stimulation serves to decrease renal medullary blood flow while V2 receptor stimulation appears to increase renal medullary blood flow; however, the net effect of AVP is to decrease renal medullary blood flow.
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PMID:Control of renal medullary blood flow by vasopressin V1 and V2 receptors. 763 93

A number of analogues of vasopressin, incorporating the substitution of D-3'-(pyridyl)-alanine in position 2, were synthesized and tested for antidiuretic (V2), vasoconstrictor (V1a) and ACTH secretory (V1b; pituitary) activities. One analogue, deamino-[D-3'-(pyridyl)-alanine2]arginine-vasopressin (abbreviated d[D-3Pal]VP) was a potent pituitary agonist, weaker antidiuretic agonist, and weak vasoconstrictor antagonist. Another analogue, [D-3'-(pyridyl)-alanine2]arginine-vasopressin, had very weak pituitary activity but no measurable antidiuretic or vasoconstrictor activity. Other D-3'-(pyridyl)-alanine-substituted analogues had only very weak activity in one or two of the bioassays. In further examination of the relationship between the actions of vasopressin on generation of cyclic AMP and secretion of ACTH in pituitary cells, the cyclic AMP responses to d[D-3Pal]VP, to another analogue of vasopressin ([Val4,D-Arg8]VP) with potent agonist activity at pituitary and renal (V2) receptors, and to CRF were compared to that of vasopressin. At the prescribed concentrations, the ACTH secretory responses to vasopressin, d[D-3Pal]VP, and [Val4,D-Arg8]VP were comparable; but only ([Val4,D-Arg8]VP) and CRF, which did not change ACTH secretion, increased intracellular cyclic AMP. These results indicate the possibility of synthesizing analogues of vasopressin with selective activity for the pituitary response and the potential for further study of vasopressin receptor subtypes, using the D-3'-(pyridyl)-alanine substitution. They are also consistent with the concept that the ACTH secretory response to vasopressin by itself is not linked to cyclic AMP, although adenylate cyclase may be activated.
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PMID:Structure--function studies of vasopressin analogues with D-3 pyridyl-alanine in position 2. 765 89

Several neuropeptides, including neurotensin, somatostatin, bradykinin, angiotensin II, substance P, and luteinizing hormone-releasing hormone but not vasopressin and oxytocin, were actively metabolized through proteolytic degradation by cultivated astrocytes obtained from rat cerebral cortex. Because phenanthroline was an effective degradation inhibitor, metalloproteases were responsible for neuropeptide fragmentation. Neurotensin was cleaved by astrocytes at the Pro10-Tyr11 and Arg8-Arg9 bonds, whereas somatostatin was cleaved at the Phe6-Phe7 and Thr10-Phe11 bonds. These cleavage sites have been found previously with endopeptidases 24.16 and 24.15 purified from rat brain. Addition of specific inhibitors of these proteases, the dipeptide Pro-Ile and N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-4-aminobenzoate, significantly reduced the generation of the above neuropeptide fragments by astrocytes. The presence of endopeptidases 24.16 and 24.15 in homogenates of astrocytes could also be demonstrated by chromatographic separations of supernatant solubilized cell preparations. Proteolytic activity for neurotensin eluted after both gel and hydroxyapatite chromatography at the same positions as found for purified endopeptidase 24.16 or 24.15. In incubation experiments or in chromatographic separations no phosphoramidon-sensitive endopeptidase 24.11 (enkephalinase) or captopril-sensitive peptidyl dipeptidase A (angiotensin-converting enzyme) could be detected in cultivated astrocytes. Because astrocytes embrace the neuronal synapses where neuropeptides are released, we presume that the endopeptidases 24.16 and 24.15 on astrocytes are strategically located to contribute significantly to the inactivation of neurotensin, somatostatin, and other neuropeptides in the brain.
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PMID:Endopeptidases 24.16 and 24.15 are responsible for the degradation of somatostatin, neurotensin, and other neuropeptides by cultivated rat cortical astrocytes. 790 52

In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.
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PMID:Prolonged stimulation of intrarenal V1 vasopressin receptors results in sustained hypertension. 797 48

Autosomal dominant neurohypophyseal diabetes insipidus is a familial form of diabetes insipidus. This disorder is associated with variable levels of arginine vasopressin (AVP) and diabetes insipidus of varying severity, which responds to exogenous AVP. To determine the molecular basis of autosomal dominant neurohypophyseal diabetes insipidus, the AVP genes of members of a large kindred were analyzed. A new method, called dideoxy fingerprinting, was used to detect an AVP mutation that was characterized by DNA sequencing. The novel defect found changes the last codon of the AVP signal peptide from alanine to threonine, which should perturb cleavage of mature AVP from its precursor protein and inhibit its secretion or action.
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PMID:Detection of a novel arginine vasopressin defect by dideoxy fingerprinting. 837 Jun 80

We studied the pathophysiology, natural history, and genetic basis of familial neurohypophyseal diabetes insipidus (FNDI) in a caucasian kindred. Twelve members had polyuria and a deficiency of plasma vasopressin (AVP), which progressed in severity over time. Another had normal urine volumes and plasma AVP when first tested at age 3 yr, but developed severe FNDI a year later. For unknown reasons, one man had a normal urine volume despite severe AVP deficiency and a history of polyuria in the past. When the AVP-neurophysin-II gene was amplified and sequenced, exon 2/3 was normal, but 7 of 12 clones of exon 1 contained a base substitution (G-->A) predicting a substitution of threonine for alanine at the -1 position of the signal peptide. Restriction analysis found the mutation in all 14 affected members, but in none of the 41 controls or 19 adult members with normal urine volumes and plasma or urinary AVP (lod score = 5.7). The mutation was also found in 2 infants in whom AVP was normal when tested at 6 and 9 months of age. We hypothesize that a mutation in exon 1 of the AVP-neurophysin-II gene causes FNDI in this kindred by making an abnormally processed precursor that gradually destroys vasopressinergic neurons.
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PMID:Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation. 837 Jun 80

The peptide encoded in the 5' to 3' direction by rat vasopressin complementary RNA, rat PVA (H-Ser-Ser-Trp-Ala-Val-Leu-Glu-Val-Ala- OH) and the corresponding bovine PVA (H-Ala-Pro-Trp-Ala-Val-Leu-Glu-Val-Ala-OH) were investigated with respect to their interaction with [8-arginine] vasopressin (AVP) and V2 vasopressin receptor binding and function. Rat or bovine PVA did neither affect the binding of the hormone to the V2 receptor of bovine kidney membranes and LLC-PK1 pig kidney cells nor influence the AVP-induced cAMP-production in LLC-PK1 cells. Rat PVA was further investigated by the use of vasopressin-specific polyclonal and monoclonal antibodies with different affinity and epitope specificity. Consistent with receptor binding studies no inhibition of [3H]AVP-binding in fluid- or solid-phase antibody binding tests after preincubation with PVA was found. Direct interaction of rat PVA and [3H]AVP measured on solid surface was not observed in contrast to specific binding of the hormone with NP II and antibodies. In our study no evidence for an interaction of AVP and its antisense peptides was found.
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PMID:Lack of interaction of vasopressin with its antisense peptides: a functional and immunological study. 838 19

Marmocets were used in a structure activity study of the ability of vasopressin analogues to activate plasminogen activator (tPA). In evaluation of dDAVP analogues with L-alanine migrating from position 2 to 9 we found [L-Ala4]dDAVP and [L-Ala5]dDAVP to be potent activators of tPA. Double substitutions in dDAVP showed that combinations of a modification in position 4 valine with a change at position 2 (2-O-methyltyrosine) generated tPA releasing activity. On the other hand enlargement of the substituent at position 2 (2-O-ethyltyrosine) completely eliminated the activity of [L-Val4]dDAVP. The tPA activity is dependent on the position of a positively charged group at the amino acid in position 8 of the peptide chain. A shift of the guanido group further away from the backbone (D-arginine to D-homoarginine) resulted in a loss of tPA activating properties.
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PMID:Tissue plasminogen activator enhancing activity of vasopressin analogues in monkeys: structure-activity study. 845 Apr 95

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.
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PMID:Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus. 851 68


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