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)

The aquaporins transport water through membranes of numerous tissues, but the molecular mechanisms for sensing changes in extracellular osmolality and regulating water balance in brain are unknown. We have isolated a brain aquaporin by homology cloning. Like aquaporin 1 (AQP1, also known as CHIP, channel-forming integral membrane protein of 28 kDa), the deduced polypeptide has six putative transmembrane domains but lacks cysteines at the known mercury-sensitive sites. Two initiation sites were identified encoding polypeptides of 301 and 323 amino acids; expression of each in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability not blocked by 1 mM HgCl2, even after substitution of cysteine at the predicted mercury-sensitive site. Northern analysis and RNase protection demonstrated the mRNA to be abundant in mature rat brain but only weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of brain localized the mRNA to ependymal cells lining the aqueduct, glial cells forming the edge of the cerebral cortex and brainstem, vasopressin-secretory neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje cells of cerebellum. Its distinctive expression pattern implicates this fourth mammalian member of the aquaporin water channel family (designated gene symbol, AQP4) as the osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.
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PMID:Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. 752 31

Analogues of arginine vasopressin (AVP) with bulky thioacid residues in position 1 of the amino acid sequence are known to be effective antagonists of the pressor response. Some of the most effective ones are those that have the first cysteine residue replaced with beta,beta-cyclopentamethylene-beta'-mercaptopropionic acid (Cpp) and its derivatives, such as 4-mercapto-4-tetrahydropyraneacetic acid (OCA) and 4-mercapto-4-tetrahydrothiopyraneacetic acid (SCA). The SCA analogues are more potent and the OCA ones slightly less potent antagonists than the Cpp ones. In this study we carried out conformational calculations on [Cpp1]AVP, [OCA1]AVP and [SCA1]AVP, using the ECEPP/3 force field both with and without hydration (to simulate an aqueous and non-polar receptor environment, respectively). It was found that most of the low-energy conformations are common in geometry and relative energy for all three compounds studied. It can therefore be concluded that the modifications of the cyclohexyl ring in position 1 influence the binding to the receptor because of changing the lipophilicity of the first residue, rather than by changing the conformational space. This is further supported by the fact that the lowest-energy conformations in the absence of water have closely located the Phe3 side chain (which is critical for the interaction with vasopressin receptors) and the (modified) cyclohexyl ring. The lowest-energy conformations in the presence and absence of water had beta-turns at residues Phe3-Gln4 and Gln4-Asn5, and Gln4-Asn5, respectively. The conformation with the turn at Gln4-Asn5 was most similar to the crystal structure of the pressinoic acid (the cyclic moiety of vasopressin).
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PMID:Theoretical conformational analysis of three vasopressin antagonists with a modified cyclohexyl ring in the first thioacid residue. 759 84

New cysteine S-sulfonate derivatives, Boc-Cys(SO3Na)-ONa 2 and Fmoc-Cys(SO3Na)-ONa 3, were prepared and their utility for peptide synthesis examined. The Fmoc derivative 3 was used in the solid-phase peptide synthesis of Arg8-vasopressin 9 via the Bunte salt 7. Satisfactory S-sulfonate stability was observed when p-cresol scavenged the cleavage from the resin. The intermediate 7 was purified by ion-exchange chromatography prior to S-sulfonate cleavage with tributylphosphine.
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PMID:Peptide synthesis using novel S-sulfocysteine derivatives. 778 63

An aminopeptidase from porcine kidney, hydrolyzing oxytocin and vasopressin in vitro, was purified by chromatography on hydroxyapatite, DEAE-cellulose and nickel ion chelate gel and gel filtration on Sephadex G-100. The enzyme appeared to be a high molecular mass (M(r) 105,000) monomeric protein. It was sensitive to inhibition by metal chelator, o-phenanthroline. Cobalt ion and sulfhydryl activator, 2-mercaptoethanol, had activating effects, while p-chloromercuribenzoate, amino acids with large hydrophobic side chains, L-cystine and aminopeptidase inhibitors, bestatin and amastatin, had inhibitory effects on the enzyme activity. The enzyme hydrolyzed several aminoacyl p-nitroanilides, and had the highest specificity against S-benzyl-L-cysteine p-nitroanilide. The properties of the enzyme were distinct from those of well-characterized leucyl aminopeptidase (EC 3.4.11.1), membrane alanyl aminopeptidase (EC 3.4.11.2) and primate placental cystinyl aminopeptidase (EC 3.4.11.3).
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PMID:An aminopeptidase activity from porcine kidney that hydrolyzes oxytocin and vasopressin: purification and partial characterization. 787 63

Cysteamine (CSH), a sulfhydryl agent that promotes disulfide-exchange reactions, was studied for its effects on the immunoreactive (IR) levels and synthesis of oxytocin and vasopressin in the hypothalamus. CSH injection (300 mg/kg s.c.) caused a rapid (1 h) suppression of 35S-cysteine incorporation into hypothalamic arginine vasopressin (VP) and oxytocin (OT). The reduction in labeling persisted for about 8 h; label incorporation was normal within 10 h of CSH administration. The drug did not influence 35S-cysteine incorporation into acid-precipitable protein, nor did it influence 35S-cysteine specific activity in the hypothalamus. In addition, 35S-VP and 35S-OT molecules could not be recovered from hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing and then reoxidizing conditions. Despite the reduction in peptide labeling, CSH treatment produced no alterations in the IR VP and OT contents of hypothalamus or posterior pituitary. These results indicate that CSH causes a true suppression of both VP and OT formation in hypothalamus, and suggest that the effect is either too transient to promote a reduction in endogenous stores of either peptide, or that the drug equally inhibits peptide production and removal (i.e., axonal transport, secretion).
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PMID:Effect of cysteamine injection on vasopressin and oxytocin biosynthesis in rat hypothalamus. 815 71

Eighteen linear analogues of [Arg8]vasopressin (AVP) were synthesized by systematically substituting the cysteine residues at positions 1 and 6 with a range of L-amino acids. Screening by competition ligand binding revealed that the combinations of amino acid residues tolerated at these positions was very restricted with respect to retention of vasopressin receptor (VPR) binding. Consequently, only three of the eighteen analogues investigated, [Pro1,Met6]AVP, [Gly1,Met6]AVP and [Phe1,Lys6]AVP, bound to the V1a receptor. Furthermore, these three peptides were all selective for the V1a receptor rather than the V1b, V2 and vasotocin receptors. In addition, although very homologous to the natural agonist, these analogues were in fact antagonists at V1a receptors. These data provide insights into the biophysical requirements at positions 1 and 6 of linear ligands for binding to V1a receptors and furthermore, supply clues to the nature of the receptor:ligand interaction.
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PMID:Pharmacological characterization of linear analogues of vasopressin generated by the systematic substitution of positions 1 and 6 by L-amino acids. 818 60

Peptide contents of neural lobes from adult jerboas (Jaculus orientalis) under different states of hydration were determined by radioimmunoassay. The amounts of vasopressin, oxytocin, and their associated neurophysins in animals dehydrated for up to 4 weeks were not significantly different from those of controls. The different neurohypophyseal peptide were separated on two different types of gradient using reverse-phase high-performance liquid chromatography. The shape of the chromatograms suggests that, in contrast to the case of the rat, for which only three types of neurophysins have been shown, there are, in jerboa, many subspecies of neurophysins. This was also shown using two-dimensional electrophoresis. Injection of [35S]cysteine into the supraoptic nucleus followed by HPLC of extracts from the neural lobes from animals under different states of dehydration showed that the labeled material is not released any faster in dehydrated animals than in controls. Labeled vasopressin, oxytocin, and neurophysins could still be detected by HPLC 4 weeks after injection. Neural lobes from animals injected with [35S]cysteine were perfused in vitro and the release of neuropeptides was triggered by bursts of electrical pulses and also by K(+)-induced depolarization. The amplitude of the rate constant for release and the amounts of vasopressin and of radiolabeled material released were similar in animals dehydrated for up to 3 weeks and in controls. Under physiological conditions similar to those that would be expected to occur in their natural habitat, the jerboas appear to have a hypothalamoneurohypophyseal system which is down-regulated.
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PMID:Synthesis, turnover, and release of peptides from the neurohypophysis of the Jerboa Jaculus orientalis. 819 37

Methodology is described for characterization of the kinetics and equilibria of thiol/disulfide interchange reactions of the disulfide bonds in the neurohypophyseal peptide hormones arginine vasopressin and oxytocin and the related peptides pressinoic acid and tocinoic acid. Thiol/disulfide interchange reaction mixtures are analyzed by reversed-phase high-performance liquid chromatography. The effect of mobile-phase composition and pH on the HPLC capacity factors for the native disulfide and reduced dithiol forms of each peptide was examined. In each case, the capacity factor decreases as the acetonitrile content of the mobile phase increases. For each disulfide/dithiol peptide pair, the capacity factor is larger for the dithiol form of the peptide, indicating that the hydrophobic side chains of the linear peptide are more accessible for interaction with the hydrophobic stationary phase. To illustrate application of the methodology, rate and equilibrium constants are reported for the thiol/disulfide interchange reactions of cysteine with arginine vasopressin at pH 7.0. Cysteine reacts with arginine vasopressin to form two mixed disulfides, which in turn react with another molecule of cysteine to give the dithiol form of arginine vasopressin and cystine. Rate and equilibrium constants were determined for each step by analysis of reaction mixtures by HPLC. The results are compared to rate and equilibrium constants for reaction of cysteine with oxidized glutathione.
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PMID:Characterization of the thiol/disulfide chemistry of neurohypophyseal peptide hormones by high-performance liquid chromatography. 825 69

Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel in the kidney collecting duct. AQP-2 is selectively permeable to water molecule and is translocated between the apical membrane and subapical endosomes in response to vasopressin. To investigate the localization and structure of the aqueous pathway of the AQP-2 water channel, a series of site-directed mutants was constructed and functionally analyzed. Insertion of N-glycosylation reporter sequence into each hydrophilic loop (HL) indicated that AQP-2 has a six-membrane spanning topology and that insertional mutations in HL-2 or HL-5 do not alter water channel function. Mercury-sensitive site of AQP-2 is located near the second asparagine-proline-alanine (NPA) domain at cysteine 181, but not near the first NPA domain. Replacement of HL-3 or HL-4 with the corresponding part of Escherichia coli glycerol facilitator abolished water channel function without changing plasma membrane expression of the channel protein. Introduction of cysteine residues in His-122, Asn-123, Gly-154, Asp-155, or Asn-156 induced partial mercury sensitivity, and point mutations in asparagine 123 significantly altered water permeability. Our results implicate that the structure of AQP-2 is different from models previously proposed for AQP-1 and that HL-3 and HL-4 are closely located to the aqueous pathway.
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PMID:Structure of aquaporin-2 vasopressin water channel. 861 98

The hemodynamic effects of intracisternal injection of the nonessential amino acid L-cysteine were studied in conscious chronically instrumented rats. Injections of L-cysteine (0.05-0.2 M in artificial cerebrospinal fluid, 10 microliters) into the cisterna magna dose-relatedly elicited an increase in arterial pressure but a decrease in superior mesenteric blood flow as measured by an electromagnetic flow probe. Injections of the excitatory amino acid transmitter L-glutamate at comparable doses caused much the same pressor and vasoconstrictor effects as did L-cysteine. Prior I.V. injection of vasopressin V1-receptor antagonist, (d(CH2)5(1), O-Me-Tyr2, Arg8)-vasopressin (10 micrograms/kg), markedly attenuated the effects of L-glutamate but not of L-cysteine. Ganglionic blockade with chlorisondamine (5.0 mg/kg) failed to attenuate the effects of either amino acid, whereas an additional intravenous injection of vasopressin antagonist, completely abolished the effects. These results indicate that the circulatory effects of L-cysteine are probably due to autonomic nervous activation combined with vasopressin release, unlike those of L-glutamate which acts mainly through vasopressin release. L-Cysteine may contribute to central cardiovascular control, since it induces the marked circulatory effects comparable to or greater than those of L-glutamate.
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PMID:The central effect of L-cysteine on cardiovascular system of the conscious rat. 871 75


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