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)

To investigate the relationship between 12 candidate genes responsible for water regulation, sodium metabolism and membrane ion transport and essential hypertension (EH) in the Chinese. Linkage analysis of EH was performed in 95 Chinese nuclear families including 477 subjects using a technique of fluorescence-based gene scanning with 12 microsatellite markers. Markers were selected on the chromosomal regions covering 12 candidate genes responsible for regulating water and sodium metabolism and membrane ion transport. These candidate genes included sodium hydrogen exchanger 3, sodium hydrogen exchanger 5, chloride bicarbonate exchanger 3, sodium calcium exchanger 1, mineralocorticoid receptor, plasma membrane calcium ATPase 2, ATPase,Na/K transporting alpha, a-adducin, SA gene, kidney epithelial sodium channel-gamma, vasopressin receptor 1A, and 11beta-hydroxysteroid dehydrogenase type 2 genes. Two-point non-parametric linkage analysis (NPL), maximum LOD score analysis and transmission/disequilibrium test (TDT) were performed using the GENEHUNTER software package. The NPL analysis and LOD score suggested a significant linkage at D12S398 (Z = 2.08, p<0.05 and LOD score = 1.26, p<0.01, respectively). TDT indicated a significant disequilibrium of transmission at the locus chi2 = 9.00, p < 0.005). No significant linkages were found at the other loci tested (p > 0.05 or LOD < -1). In conclusion, D12S398, a marker near the vasopressin receptor 1A gene (V1AR), showed a positive linkage with EH based on the results of three statistical methods (NPL, LOD score, and TDT). This region warrants further exploration.
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PMID:Linkage analysis of twelve candidate gene loci regulating water and sodium metabolism and membrane ion transport in essential hypertension. 1235 53

The endothelial cell layer displays the features of a distributed organ and has a variety of biological functions such as keeping the balance between coagulation and fibrinolysis, expression of adhesion molecules for cells in the immune system, metabolism of noradrenaline and 5-hydroxytryptamine, and conversion of angiotensin I and bradykinin. The endothelium also regulates the underlying smooth muscle layer and vascular tone by release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) as well as vasoconstricting factors such as endothelin, superoxide (O(2)(-)), and thromboxane. We have reviewed the nature, mechanisms of action, and role of these factors in regulation of vascular tone, with special emphasis on NO. By a process catalyzed by NO synthase, NO and citrulline is formed from the substrates molecular O(2) and L-arginine. The main receptor for NO is guanylyl cyclase leading to formation of smooth muscle cyclic guanosinmonophosphate and relaxation. EDHF is an endothelium-derived factor causing vasorelaxation of the underlying smooth muscle layer by hyperpolarization. The nature of EDHF is still unknown, but several candidates for EDHF have been proposed such as potassium ions, hydrogen peroxide, and epoxyeicosatrienoic acids. Prostaglandins such as prostacyclin and prostaglandin E2 binds to specific receptors followed by increases in cyclic adenosinmonophosphate and vasorelaxation, while contractile prostaglandins constrict vessels by activation of thromboxane and endoperoxidase receptors. Superoxide anions induce contraction of vascular smooth muscles cells by scavenging NO. Endothelin is a potent endothelium-derived contractile factor. The synthesis of endothelin-1 is induced by hypoxia, thrombin, interleukin-1, transforming growth factor-beta1, vasopressin, and catecholamines. Cardiovascular risk factors like age, hypertension, and hyperlipidemia are associated with impaired endothelium-dependent vasodilation either as a consequence of increased inactivation of endothelium-derived vasodilators or increased formation of endothelium-derived contracting factors. This imbalance of endothelium-derived factors plays a role for development of atheroslerosis and ischemic vascular diseases.
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PMID:[Role of nitric oxide and other endothelium-derived factors]. 1273 1

Ceftiofur is an important veterinary beta-lactam antibiotic whose bioactive metabolite, desfuroylceftiofur, has a free thiol group. Desfuroylceftiofur (DFC) was reacted with two peptides, [Arg8]-vasopressin and reduced glutathione, both of which have cysteine residues to form disulfide-linked peptide/antibiotic complexes. The products of the reaction, [vasopressin + (DFC-H) + (DFC-H) + H]+, [(vasopressin+H) + (DFC-H) + H]+ and [(glutathione-H) + (DFC-H) + H]+, were analyzed using collision-activated dissociation (CAD) with a quadrupole ion trap tandem mass spectrometer. MS/MS of [vasopressin + (DFC-H) + (DFC-H) + H]+ resulted in facile dissociative loss of one and two covalently bound DFC moieties. Loss of one DFC resulted from either homolytic or heterolytic dissociation of the peptide/antibiotic disulfide bond with equal or unequal partitioning of the two sulfur atoms between the fragment ion and neutral loss. Hydrogen migration preceded heterolytic dissociation. Loss of two DFC moieties from [vasopressin + (DFC-H) + (DFC-H) + H]+ appears to result from collision-activated intramolecular disulfide bond rearrangement (IDBR) to produce cyclic [vasopressin + H]+ (at m/z 1084) as well as other cyclic fragment ions at m/z 1084 +/- 32 and +64. The cyclic structure of these ions could only be inferred as MS/MS may result in rearrangement to non-cyclic structures prior to dissociative loss. IDBR was also detected from MS(3) experiments of [vasopressin + (DFC-H) + (DFC-H) + H]+ fragment ions. MS/MS of [(glutathione-H) + (DFC-H) + H]+ resulted in cleavage of the peptide backbone with retention of the DFC moiety as well as heterolytic cleavage of the peptide/antibiotic disulfide bond to produce the fragment ion: [(DFC-2H) + H]+. These results demonstrate the facile dissociative loss by CAD of DFC moieties covalently attached to peptides through disulfide bonds. Published in 2004 by John Wiley & Sons, Ltd.
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PMID:Collision-activated cleavage of a peptide/antibiotic disulfide linkage: possible evidence for intramolecular disulfide bond rearrangement upon collisional activation. 1505 80

Water constitutes approximately 60% of the healthy adult human body. Water balance in the body is regulated by the kidneys, which excrete either concentrated or dilute urine in accordance with physiological needs. This article describes the mechanisms by which the kidneys vary water excretion independent of excretion of other physiological important substrates such as sodium, potassium, hydrogen, and urea. These mechanisms involve the loops of Henle, the distal tubules, the collecting ducts, and the vasa recta, and are under the control of vasopressin (antidiuretic hormone).
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PMID:Urinary concentration and dilution. 1530 25

Molecular and pathogenetic mechanisms in sodium retention and water reabsorption of nephrotic edema are discussed. Are reported and analyzed molecular mechanisms about sodium retention in collecting duct cells regarding activation and surface expression of epithelial sodium channels (ENaC) and sodium-potassium-ATPase (Na,K-ATPase) by aldosterone, vasopressin, natriuretic peptide system (underfill theory): is necessary a better understanding about the dysregulation of ENaC and Na,K-ATPase surface expression and the resistance to natriuretic peptide system. Are also reported and analyzed molecular mechanisms of sodium retention in proximal tubule cells regarding intrinsic albumin toxicity upon type 3 sodium-hydrogen exchanger ionic pump and the activity of sodium-hydrogen exchanger regulatory factor protein (overfill theory): a better knowledge about the link between albumin, sodium-hydrogen exchanger type 3 (NHE3) ionic pump, sodium-hydrogen exchanger regulatory factor protein is necessary. Then molecular mechanisms of vasopressin free water retention through acquaporin water channels in collecting duct cells are discussed: further studies are necessary to understand vasopressin release pathway (osmotic/nonosmotic) and V2 receptor activation with cell surface expression of renal acquaporins water channel.
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PMID:Molecular pathogenetic mechanisms of nephrotic edema: progress in understanding. 1589 43

The vasopressin V2 receptor (V2R) belongs to the Class A G protein-coupled receptors (GPCRs). V2R is expressed in the renal collecting duct (CD), where it mediates the antidiuretic action of the neurohypophyseal hormone arginine vasopressin (CYFQNCPRG-NH2, AVP). Desmopressin ([1-deamino, 8-D]AVP, dDAVP) is strong selective V2R agonist with negligible pressor and uterotonic activity. In this paper, the interactions responsible for binding of dDAVP to vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors has been examined. Three-dimensional activated models of the receptors were constructed using the multiple sequence alignment and the complex of activated rhodopsin with Gt(alpha) C-terminal peptide of transducin MII-Gt(alpha) (338-350) prototype (Slusarz, R.; Ciarkowski, J. Acta Biochim Pol 2004 51, 129-136) as a template. The 1-ns unconstrained molecular dynamics (MD) of receptor-dDAVP complexes immersed in the fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) membrane model was conducted in an Amber 7.0 force field. Highly conserved transmembrane residues have been proposed as being responsible for V2R activation and G protein coupling. Molecular mechanism of the dDAVP binding has been suggested. The internal water molecules involved in an intricate network of the hydrogen bonds inside the receptor cavity have been identified and their role in the stabilization of the agonist-bound state proposed.
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PMID:Investigation of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors: molecular dynamics simulation of the agonist-bound state in the membrane-aqueous system. 1633 59

Current evidence indicates that the ligand-facilitated dimerization of neurophysin is mediated in part by dimerization-induced changes at the hormone binding site of the unliganded state that increase ligand affinity. To elucidate other contributory factors, we investigated the potential role of neurophysin's short interdomain loop (residues 55-59), particularly the effects of loop residue mutation and of deleting amino-terminal residues 1-6, which interact with the loop and adjacent residues 53-54. The neurophysin studied was bovine neurophysin-I, necessitating determination of the crystal structures of des 1-6 bovine neurophysin-I in unliganded and liganded dimeric states, as well as the structure of its liganded Q58V mutant, in which peptide was bound with unexpectedly increased affinity. Increases in dimerization constant associated with selected loop residue mutations and with deletion of residues 1-6, together with structural data, provided evidence that dimerization of unliganded neurophysin-I is constrained by hydrogen bonding of the side chains of Gln58, Ser56, and Gln55 and by amino terminus interactions, loss or alteration of these hydrogen bonds, and probable loss of amino terminus interactions, contributing to the increased dimerization of the liganded state. An additional intersubunit hydrogen bond from residue 81, present only in the liganded state, was demonstrated as the largest single effect of ligand binding directly on the subunit interface. Comparison of bovine neurophysins I and II indicates broadly similar mechanisms for both, with the exception in neurophysin II of the absence of Gln55 side chain hydrogen bonds in the unliganded state and a more firmly established loss of amino terminus interactions in the liganded state. Evidence is presented that loop status modulates dimerization via long-range effects on neurophysin conformation involving neighboring Phe22 as a key intermediary.
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PMID:Contributions of the interdomain loop, amino terminus, and subunit interface to the ligand-facilitated dimerization of neurophysin: crystal structures and mutation studies of bovine neurophysin-I. 1719 88

A monolithic column was prepared using l-phenylalanine as template and a covalent approach through the formation of Schiff base with o-phthalaldehyde (OPA). OPA, allylmercaptan, l-phenylalanine, and triethylamine were stirred at first, then methacrylic acid, 2-vinylpyridine, ethyleneglycol dimethacrylate, alpha,alpha-azobisisobutyronitrile, and 1-propanol were added to the reaction mixture. The resulting material was introduced into a capillary column. Following thermal polymerization, the template was then extracted with a mixture of HCl and methanol. The column was employed for the capillary electrochromatographic separation of oligopeptides. A capillary column of 75 (50) cm x 75 microm ID with a mobile phase of phosphate buffer (pH 7.0, 40 mM)/methanol (5%, v/v), an applied voltage of +15 kV, and detection at 214 nm, could baseline separate angiotensin I, angiotensin II, [Sar1, Thr8] angiotensin, oxytocin, vasopressin, tocinoic acid, beta-casomorphin bovine, beta-casomorphin human, and FMRF amide within 20 min. The separation behavior of the templated polymer was also compared with that of the non-templated polymer. As a result, it can be concluded that the electrochromatographic separation of this set of peptides was mediated by a combination of electrophoretic migration and chromatographic retention involving hydrophobic, hydrogen bonding, electrostatic as well as the Schiff base formation with OPA in the cavity of the templated polymer.
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PMID:A novel monolithic column for capillary electrochromatographic separation of oligopeptides. 1772 78

Bone loss resulting from chronic ethanol (EtOH) abuse is frequently accompanied by altered vitamin D3 homeostasis. In the current study, we examined EtOH effects in a female rat model in which control or EtOH-containing diets were infused intragastrically. EtOH treatment reduced plasma 1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) coincident with a decrease in renal CYP27B1 (25(OH)D3 1alpha-hydroxylase) mRNA and an increase in expression of renal CYP24A1 (1,25 (OH)2 D3- 24-hydroxylase). EtOH induction of CYP24A1 occurred as a result of increased transcription and was also observed in vitro in primary cultures of rat renal proximal tubule cells (RPTCs) and in NRK-52E cells. Synergistic induction of CYP24A1 by EtOH in combination with 1,25 (OH)2 D3 was observed. The major EtOH metabolizing enzymes, alcohol dehydrogenase-1 and CYP2E1, were induced by EtOH in RPTCs. Inhibition of EtOH metabolism by 4-methylpyrazole inhibited the induction of CYP24A1 mRNA. CYP24A1 mRNA induction in RPTCs was also inhibited by the protein synthesis inhibitor cycloheximide. CYP24A1 was also induced after hydrogen peroxide treatment, and EtOH treatment of RPTCs resulted in production of reactive oxygen species as measured by flow cytometry using the fluorescent probe dichlorofluorescin acetate. In addition, inhibition of MAPK signaling pathways with the MAPK kinase inhibitor U0126 or the p38 inhibitor SB203580 inhibited EtOH induction of CYP24A1. Our data suggest that EtOH reduces circulating 1,25 (OH)2 D3 concentrations as the result of CYP24A1 induction that is mediated via MAPK activation resulting from renal oxidative stress produced by local metabolism of EtOH via CYP2E1 and antidiuretic hormone-1.
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PMID:Chronic ethanol consumption leads to disruption of vitamin D3 homeostasis associated with induction of renal 1,25 dihydroxyvitamin D3-24-hydroxylase (CYP24A1). 1816 28

We report a new method for identifying disulfide linkages in peptides using mass spectrometry. This is accomplished by collisional activation of singly charged cationic alkali and alkaline earth metal complexes, which results in the highly selective elimination of hydrogen disulfide (H2S2). Complexes of peptides possessing disulfide bonds with sodium and alkaline earth metal are generated using electrospray ionization (ESI). Isolation followed by collision induced dissociation (CID) of singly charged peptide complexes results in selective elimination of H2S2 to leave newly formed dehydroalanine residues in the peptide. Further activation of the product yields sequence information in the region previously short circuited by the disulfide bond. For example, singly charged magnesium and calcium ion bound complexes of [Lys8]-vasopressin exhibit selective elimination of H2S2 via low-energy CID. Further isolation of the product followed by CID yields major b- and z-type fragments revealing the peptide sequence in the region between the newly formed dehydroalanine residues. Numerous model peptides provide mechanistic details for the selective elimination of H2S2. The process is initiated starting with a metal stabilized enolate anion at Cys, followed by cleavage of the S-C bond. An examination of the peptic digest of insulin provides an example of the application of the selective elimination of H2S2 for the identification of peptides with disulfide linkages. The energetics and mechanisms of H2S2 elimination from model compounds are investigated using density functional theory (DFT) calculations.
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PMID:Identifying the presence of a disulfide linkage in peptides by the selective elimination of hydrogen disulfide from collisionally activated alkali and alkaline earth metal complexes. 1818 21


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