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 inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the "Post-Proline Cleaving Enzyme", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal.
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PMID:Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species. 0

Purified collagenase of Clostridium histolyticum was shown to cleave reduced and S-carboxamidomethylated bovine neurophysin between Cys-13 and Gly-14. The scission resulted in formation of two separable fragments: a smaller peptide arising from residues 1 through 13, and a larger peptide comprising the remainder of the residues of the protein. By dansylation procedures, the smaller peptide was shown to have amino-terminal alanine as expected from the sequence of neurophysin II, and the larger peptide had amino-terminal glycine as anticipated. These results show that collagenase indeed cleaves bovine neurophysin II in accord with the specificity postulated for that enzyme, i.e., scission between -X-Gly- in a sequence of -Pro-X-Gly-Pro-Y-. This result, obtained with a non-collagenous protein substrate, is further confirmation of the specificity of collagenase as established by its action on collagens and on synthetic oligopeptides.
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PMID:Specific cleavage of reduced and S-carboxamidomethylated neurophysin II by the collagenase of Clostridium histolyticum. 20 39

The NH exchange rates in aqueous media of oxytocin and 8-lysine vasopressin (LVP) have been measured by using transfer of solvent saturation method. The data are consistent with a "highly motile" dynamic equilibrium between folded and highly solvated conformations. The highly-motility limit applies to the exchange of NH hydrogens of oxytocin and LVP. Folded structures are more prevalent in oxytocin than in LVP. Partial shielding is indicated for peptide hydrogens of Asn5 and perhaps also Cys6 of oxytocin and for Cys6 of LVP. It is tentatively proposed that the folded conformation of oxytocin in aqueous media may contain a parallel beta-structure in the tocinamide ring consisting of two hydrogen bonds: one between the Tyr2 C = O and Asn5 peptide NH as originally proposed for the preferred conformation of oxytocin in dimethyl sulfoxide (D. W. Urry and R. Walter), and the second between he Cys1 C = O and the Cys6 NH. In LVP the hydrogen bond between the Tyr2 C = O and Asn5 peptide NH appears to be absent. The acylic tripeptide sequences (-Pro-X-Gly-NH2) of both hormones appear to be predominantly solvated. The second-order rate constants for acid catalyzed exchange of the primary amide hydrogens of Gln4, Asn5, and Gly9 of oxytocin are consistently greater for the trans NH than for the corresponding cis NH. This observation can be rationalized in terms of mechanisms involving protonation of either the amide oxygen, or the amide nitrogen, but with limited rotation about the C - N bond.
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PMID:Amide hydrogen exchange rates of peptides in H2O solution by 1H nuclear magnetic resonance transfer of solvent saturation method. Conformations of oxytocin and lysine vasopressin in aqueous solution. 26 22

The peptide Z-Pro-Leu-Gly-NH2 attenuated puromycin-induced amnesia in mice when administered 5 days prior to training, while arginine vasopressin, lysine vasopressin and cyclo(Leu-Gly), were effective when given 24 hr before training. The activity of all peptides to inhibit puromycin-induced amnesia decreased as the interval after training and before peptide administration increased, suggesting that the peptides influence memory processes rather than generalized arousal mechanisms.
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PMID:ADH and related peptides: effect of pre- or posttraining treatment on puromycin amnesia. 62 82

Neurophysin (Np) is generally found in close association with vasopressin and oxytocin in the hypothalamo-neurohypophyseal complex. Dog neurophysin I and II have been isolated from fresh and frozen posterior pituitaries. The proteins were characterized on the basis of disc electrophoresis, immunological properties, amino acid composition and partial sequence determination. The amino terminal sequence of dog Np I is Ala-Ala-Leu-Asp-Leu-Asp-Val-Arg-Gln-Cys-Leu-Pro-Cys-Gly-Pro-Gly-Gly-Gln-Gly-while that of dog Np-II is Ala-Met-Ser-Asp-Leu-Glu-Leu. The dog Np I appears to be metabolically less stable than Np II. Isotope experiments with [35S]cystine or 3H-labeled amino acids using a design of "in vitro pulse and in vitro chase" as well as "in vivo pulse and in vivo chase," added further confirmation of the capability of the hypothalamic neurosecretory cells to synthesize concomitantly precursors of Np and vasopressin. The radioactively labeled precursors were converted to Np-like protein and vasopressin, both of which were isolated.
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PMID:Biosynthesis of neurophysin proteins in the dog and their isolation. 83 May 36

Neurohypophyseal hormones and several of their analogs, as well as N-terminal and C-terminal fragments, have been studied for their ability to attenuate puromycin-induced amnesia in mice. [8-Lysine]vasopressin, [8-arginine]vasopressin, and the analogs des-9-glycinamide-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-lysine]vasopressin, [1,6-aminosuberic acid, 8-lysine]vasopressin, [4-leucine, 8-lysine]vasopressin, glycyl-glycyl-glycyl-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-D-arginine]vasopressin, and [1,6-aminosuberic acid, 8-arginine]vasopressin are active. [8-Arginine]oxytocin as well as oxytocin and all of its other analogs tested are inactive with the striking exception of glycyl-glycyl-glycyl-oxytocin. The structural aspects of the neurohypophyseal hormones which appear to be important for significant activity in memory consolidation include the combination of a cyclic moiety containing the Tyr and Phe residues along with a basic residue in position 8. Another series of active compounds comprises C-terminal neurohypophyseal peptides and analogs thereof, including the naturally occurring Pro-Leu-Gly-NH2 and, most surprisingly, Leu-Gly-NH2, as well as its derivatives D-Leu-Gly-NH2 and the diketopiperazine, cyclo(-Leu-Gly-).
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PMID:Neurohypophyseal hormones, analogs, and fragments: their effect on puromycin-induced amnesia. 106 98

Arginine-vasopressin and oxytocin, both 14C-labeled in the glycine residue, are enzymatically inactivated by rat kidney supernatant. Production of radioactive metabolites of each hormone was followed as a function of time. Both oxytocin and vasopressin are degraded by an enzyme which cleaves their Pro-X bonds, to release Leu-Gly-NH2 from oxytocin and Arg-Gly-NH2 from vasopressin. In addition, oxytocin alone is degraded rapidly by a chymotrypsin-like enzyme which directly releases Gly-NH2 from the hormone. The direct release of Gly-NH2 from vasopressin in the homogenate is of minor importance, but there occurs a transient formation of an uncharacterized fragment in significant amounts. The data are interpreted to indicate that the difference in the overall mechanism of inactivation of the two hormones by the rat kidney extract is a result of the high level of the enzymic activity which releases Gly-NH2 directly from oxytocin, compared to the low level of activity releasing Gly-NH2 directly from the antidiuretic hormone. This allows, in the case of arginine vasopressin, a greater expression of the activity of enzyme(s) giving rise to uncharacterized fragment(s) and of the Pro-X cleaving enzyme.
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PMID:Differences in the enzymatic inactivation of arginine vasopressin and oxytocin by rat kidney homogenate. 111 88

[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin was prepared from beta-Mpa(beta-(CH2)5)(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by removal of the Bzl-protecting groups with Na-NH3 followed by cyclization of the resulting disulfhydryl compound with K3Fe(CN)6.The analog was purified by desalting on Sephadex G-15 in 50% HOAc and gel filtration on Sephadex G-25 and LH-20. The protected intermediate above was synthesized from Z-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwose p-nitrophenyl ester method using Nalpha-Boc protection at the penta-, hexa-, and octapeptide stages. The analog was found to be a potent inhibitor of the oxytocic and avian vasodepressor effects of oxytocin (pA2 values of 7.43 and 8.30, respectively) but was only a weak inhibitor of the rat pressor effect of 8-lysine-vasopressin. The rat antipressor potency of [1-deaminopenicillamine]oxytocin was also determined in this study: pA2 = 6.27. Of the alkyl-substituted 1-position analogs of oxytocin studied so far, [1-beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin is the most potent antioxytocic agent.
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PMID:[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin, a potent inhibitor of oxytocin. 113 19

[4-Phenylalanine]oxytocin was prepared from Z-Cys(Bzl)-Tyr(Bzl)-Ile-Phe-Asn-Cys(Bzl)-Pro-Leu-Gly-NG2 (4) by deprotection with Na in NH3 followed by cyclization of the resulting disulfhydryl compound with ICH2CH2I. The protected peptide 4 was prepared from Boc-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwise solution method. Coupling was effected by a modification of the dicyclohexylcarbodiimide-1-hydroxybenzotriazole preactivation method wherein the precipitate of dicyclohexylurea is removed by filtration prior to mixing of the amino and carboxyl components. The analog was found to be an effective inhibitor of the antidiuretic (ADH) response to exogenous arginine-vasopressin. It produced marked diuresis in the anti-ADH assay at approximately the same dose level as does [Leu4]oxytocin but, in contrast to [Leu4]oxytocin, showed natriuretic activity only at relatively high dose levels. In addition, [Phe4]oxytocin exhibited 0.15% of the oxytocic potency of oxytocin, weak antiavian vasodepressor activity (pA2 = 6.93), and no measurable rat pressor activity.
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PMID:(4-Phenylalanine)oxytocin, an inhibitor of the antidiuretic effect of 8-arginine-vasopressin. 115 80

[3-beta-(2-Thienyl)-L-alanine]-8-lysine-vasopressin was synthesized by solution techniques. The partially protected heptapeptide Boc-Cys(Ec)-Tyr-Thi-Gln-Asn-Cys(Ec)-Pro (1) was synthesized in a stepwise manner using the active ester method or the dicyclohexylcarbodiimide (DCC) coupling technique mediated by 1-hydroxybenzotriazole (HBt). The protected nonapeptide amide Boc-Cys(Ec)-Tyr-Thi-Gin-Asn-Cys(Ec)-Pro-Lys(Coc)-Gly-NH2 (2) was prepared by coupling 1 with Lys(Coc)-Gly-NH2 using DCC-HBt. From 2, [3-thienylalanine]-8-lysine-vasopressin was obtained by removing the Boc-protecting groups with trifluoroacetic acid and ethylcarbamoyl (Ec) protecting groups in refluxing liquid NH3 followed by oxidative cyclization in H2O-MeOH using ICH2CH2I. Purification was effected by partition chromatography followed by gel filtration. The highly purified product possesses activities in the oxytocic, avian vasodepressor, rat pressor, and antidiuretic assays of 19.0 +/- 0.5, 87 +/- 4, 243 +/- 5, and 332 +/- 32 units/mg, respectively. Thus [3-thienylalanine]-8-lysine-vasopressin has higher oxytocic, avian vasodepressor, and antidiuretic potencies than does 8-lysine-vasopressin, whereas its pressor potency is about the same as or slightly lower than that of 8-lysine-vasopressin.
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PMID:Synthesis and some pharmacological properties of (3-beta-(2-thienyl)-L-alanine)-8-lysine-vasopressin. 117 84


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