Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As part of a program in which we are attempting (a) to obtain more potent and/or more selective antagonists of the antidiuretic responses to arginine-vasopressin (AVP) and (b) to delineate the structural features at positions 1-9 required for antidiuretic antagonism, we have synthesized 13 new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-D-isoleucine,4- valine]arginine-vasopressin [d(CH2)5[D-Ile2]VAVP] in which the valine residue at position 4 has been replaced by the L-amino acids Abu, Ile, Thr, Ala, Ser, Nva, Gln, Leu, Lys, Cha, Asn, Orn, and Phe and two new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-D-phenylalanine,4- valine]arginine-vasopressin [d(CH2)5[D-Phe2]VAVP] with the Val4 residue replaced by Ser and Orn. These analogues are 1, d(CH2)5[D-Ile2,Abu4]AVP; 2, d(CH2)5[D-Ile2,Ile4]AVP; 3, d(CH2)5[D-Ile2,Thr4]AVP; 4, d(CH2)5[D-Ile2,Ala4]AVP; 5, d(CH2)5[D-Ile2,Ser4]AVP; 6, d(CH2)5[D-Ile2,Nva4]AVP; 7, d(CH2)5[D-Ile2]AVP; 8, d(CH2)5[D-Ile2,Leu4]AVP; 9, d(CH2)5[D-Ile2,Lys4]AVP; 10, d(CH2)5[D-Ile2,Cha4]AVP; 11, d(CH2)5[D-Ile2,Asn4]AVP; 12, d(CH2)5[D-Ile2,Orn4]AVP; 13, d(CH2)5[D-Ile2,Phe4]AVP; 14, d(CH2)5[D-Phe2,Ser4]AVP; and 15, d(CH2)5[D-Phe2,Orn4]AVP. The protected peptide precursors for these peptides were prepared by the solid-phase method, followed by ammonolytic cleavage. The free peptides 1-15 were obtained by deblocking with Na in NH3, oxidation of the resultant disulfhydryl compounds with dilute K3[Fe(CN)6], and purification on Sephadex G-15 in a two-step procedure with 50% HOAc and 0.2 M HOAc as eluants. Analogues 1-15 were tested in rats for agonistic and antagonistic activities by antidiuretic, vasopressor, and oxytocic assays.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Potent and selective antagonists of the antidiuretic responses to arginine-vasopressin based on modifications of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-D-isoleucine,4- valine]arginine-vasopressin at position 4. 670 45

Antidromically identified paraventricular neurones were recorded simultaneously with intramammary pressure in urethane (1.2 g/kg) anaesthetized rats during suckling. The correlation of the firing pattern of these neurones with milk ejection enabled distinction between oxytocin and vasopressin neurones. Oxytocin neurones displayed a short (2-6 s) characteristic high-frequency burst of spikes. This activation probably occurred simultaneously in all oxytocin neurones 12-18 s before milk ejection and was regular in both frequency and amplitude (total number of spikes). The role of neurohypophysial peptides and analogues in the control of these characteristics was studied. Injecting 10 pg, 100 pg and 1 ng of oxytocin into the 3rd ventricle increased background activity of slow-firing oxytocin neurones (less than 3 spikes/s) and had a strong dose-dependent facilitatory effect on the milk ejection reflex, increasing both the amplitude and frequency of neurosecretory bursts. No effect was observed on non-neurosecretory neurones. Such injection also triggered the milk ejection reflex when it had not appeared an hour after suckling began. Oxytocin did not itself induce neurosecretory activation, which only appeared if the young rats were sucking. Injecting oxytocin into the lateral ventricle was less effective than into the 3rd ventricle. No effect was observed after injection into the venous blood or into the 4th ventricle, which suggested that oxytocin acts in the hypothalamus. Injecting mesotocin or isotocin into the 3rd ventricle had a facilitatory effect similar to that of oxytocin but vasopressin, vasotocin, MIF I (pro-leu-gly-NH2, terminal triplet oxytocin) or bovine neurophysins I and II did not modify neurosecretory activation or the milk ejection pattern. Injecting an oxytocin antagonist, ([1(beta-mercapto-beta, beta cyclopentamethylene propionic acid), 8-ornithine] vasotocin, d(CH2)5OVT) into the 3rd ventricle decreased milk ejection frequency and considerably delayed the reappearance of the first milk ejection. This resulted from a decrease in both frequency and amplitude of neurosecretory bursts, which were too small to induce detectable oxytocin release. Moreover, d(CH2)5OVT suppressed the facilitatory effect of exogenous oxytocin. Under normal conditions, endogenous oxytocin seemed to be involved in the control of neurosecretory activation. Injecting 1 ng oxytocin or 1 or 10 ng vasopressin into the 3rd ventricle did not modify the firing pattern of vasopressin neurones whether activated by hyperosmotic stimulation (1 ml NaCl, 9% solution (w/v) I.P.) or not.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Electrophysiological evidence for facilitatory control of oxytocin neurones by oxytocin during suckling in the rat. 674 98

Analogs of [arginine8]vasopressin (AVP) in which the peptide chain was elongated from the N-terminus by the addition of Ala-Arg-Arg-, Ala-Ala-Phe-, Pro-Arg-Val-, Pro-Ala-Arg-Arg, and Pro-Ala-Ala-Phe-, and from the C-terminus by the addition of -Ala-Met-Ala-NH2 and -Gly-Arg-Arg-Ala-NH2 were synthesized by the solid phase method and purified by Sephadex G-15 chromatography. At the final step of the synthesis, the extent of formation of the intramolecular disulfide bond was found to be sequence dependent. These peptides were incubated with extracts of the rat hypothalamus (supraoptic region) and neural lobe and with isolated neurosecretory granules from the neural lobe, and the release of vasopressin was measured by the rat pressor assay. All peptides resisted conversion to the hormone in the presence of tissue extracts, except (Ala-Ala-Phe)-AVP which was converted to AVP in the presence of all three tissue extracts at pH 4.7 but not at pH 8.0. When these peptides were treated with trypsin, chymotrypsin, or leucine aminopeptidase at pH 8.0, only the action of chymotrypsin on [Ala-Ala-Phe]AVP resulted in AVP formation. Evidence obtained using lysosomal enzyme markers suggested that the converting enzyme activity in neurosecretory granule preparations was not of lysosomal origin.
 ...
PMID:Extended chain analogs of [arginine8]vasopressin as model prohormones: investigation of precursor-processing enzymes in extracts of the rat hypothalamus and neural lobe. 675 99

Carboxamidopeptidase, an enzyme which inactivates neurohypophyseal hormones, has been purified 3800-fold in an overall yield of 22% from toad skin, a neurohypophyseal hormone target organ, by (NH4)2SO4 fractionation, DEAE-Sephadex chromatography, and affinity chromatography on immobilized p-aminobenzamidine and concanavalin A-agrose. The purified enzyme is capable of inactivating both [8-arginine]vasopressin (AVP) and oxytocin by hydrolyzing the Arg8-Gly9-NH2 and the Leu8-Gly9-NH2 bonds, respectively, and can hydrolyze the ester substrates, benzoyl-L-arginine ethyl ester (BzArgOEt) and acetyl-L-trypsine ethyl ester, suggesting that the enzyme has both trypsin-like and chymotrypsin-like activities. Carboxamidopeptidase is maximally active at pH 7.5-8.5 for AVP and BzArgOEt and pH 7.0 for oxytocin. Carboxamidopeptidase is inhibited by ovoinhibitor, ovomucoid, Trasylol. lima bean trypsin inhibitor, concanavalin A, antipain, leupeptin, chymostatin, elastatinal, p-nitrophenyl p-guanidinobenzoate, and 4-methylumbelliferyl p-guanidinobenzoate but not by soybean trypsin inhibitor, alpha 1-antitrypsin, hirudin, pepstatin, bestatin, phosphoramidon, or cysteine. The enzyme is also inhibited by the serine protease inhibitor, diisopropyl phosphofluoridate (i-Pr2PF), and by the chloromethyl ketone derivatives of tosyllysine, tosylphenylalanine, and (benzyloxycarbonyl)phenylalanine, as well as by the sulfhydryl group reagent, p-(chloromercuri)benzoate (PCMB). Inhibition by PCMB is reversed by cysteine. The molecular weight determined by gel filtration in the presence of 1 MNaCl is approximately 100 000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the enzyme is composed of two identical subunits of 48 000 daltons. Each subunit consists of a heavy chain (28 000 daltons) and a light chain (19 000 daltons) joined by a disulfide bond(s). Labeling experiments using [3H]-i-Pr2PF showed that the enzyme active site is located in the heavy chain.
 ...
PMID:Carboxamidopeptidase: purification and characterization of a neurohypophyseal hormone inactivating peptidase from toad skin. 676 14

The biochemical characterization of a diuretic neurohormone, immunologically related to the mammalian vasopressin (AVP) and present in Locusta migratoria has been performed. The results have been obtained using an AVP radioimmunoassay as method of detection and quantification. The "AVP like" molecule exhibits the same C terminal moiety: the tetrapeptide 1/2 Cys-PrO-Arg-Gly NH2. 125I-radiolabelling allows us to demonstrate the presence of a tyrosyl residue. The molecular weight of this molecule is estimated by gel filtration to 2500 +/- 400 Daltons. The isoelectric point is 7.5 and the electrophoretic migration lead to conclude to the presence of amino acid residues lacking in the vasopressin hormone. We have demonstrated the presence of a vasopressin sequence included in high molecular weight protein which have been quantified in suboesophageal ganglion (biosynthetic site) and in the nervous ventral cord (release site).
 ...
PMID:Biochemical characterization of a vasopressin-like neuropeptide in Locusta migratoria. Evidence of high molecular weight protein encoding vasopressin sequence. 686 18

Previous hydrodynamic studies [Rholam, M., & Nicolas, P. (1981) Biochemistry 20, 5837-5843] have demonstrated that the dimerization of a neurophysin monomer (prolate ellipsoid with an axial ratio, due to asymmetry, of 5.2) results in a decreased asymmetry (axial ratio, due to asymmetry, of 3.6) as the consequence of a side-by-side association process. By a combination of hydrodynamic measurements, including the use of sedimentation velocity, viscometry, and fluorescence polarization spectroscopy, the influence of hormone binding on the shape and asymmetry properties of the neurophysin dimer was evaluated. The binding of ocytocin, vasopressin, and the tripeptide analogue of the N-terminal sequence of ocytocin, Cys(S-Me)-Tyr-Ile-NH2, results in an increase of S020,W and a decrease in both the reduced viscosity and rotational relaxation time of the bis-liganded dimeric species vs. the nonliganded form. The axial ratio (a/b) due to asymmetry of the ligand-bound dimers was found in each case to be equal to, or slightly greater than, 1.0, indicating a compact spherical shape (Stokes radius 21 A). The profound alteration on molecular dimensions observed upon ligand binding is shown to be the consequence of a ligand-induced conformational change and might explain the intradimeric binding sites positive cooperativity. It is tentatively proposed that the pseudospherical shape of the neurophysin-hormone complexes may enhance the stability of neurophysin and contribute to the prevention of leakage of neuropeptides through the membrane of neurosecretory granules. The data provide a remarkable example of a small protein with a high content in disulfide links and that undergoes conspicuous changes in conformation under the influence of nonapeptide, or tripeptide, ligands.
 ...
PMID:Binding of neurohypophyseal peptides to neurophysin dimer promotes formation of compact and spherical complexes. 713 41

The effect of vasopressin analogues dAVP, dDAVP, and desgly NH2 dDAVP on working memory was tested in the 24-arm radial maze in twelve 6-month-old and twelve 19-month-old rats. No age dependent effects were found. All three peptides tested (3 micrograms/kg) tended to improve the performance but only the desgly NH2 dDAVP significantly decreased the number of errors. A second application of desgly NH2 dDAVP was ineffective. The specificity of activation of memory mechanisms by desgly NH2 dDAVP can be questioned.
 ...
PMID:Vasopressin analogues and spatial working memory in the 24-arm radial maze. 717 19

[Ile3, Arg8]vasopressin (arginine-vasotocin), as well as the C-terminal tripeptides of the neurohypophyseal hormones arginine and lysine vasopressin, Pro-Arg-Gly-NH2 and Pro-Lys-Gly-NH2, were protective against puromycin-induced amnesia in mice when administered 24h before training. The N-protected tripeptide derivative, Z-Pro-Lys-Gly-NH2, was effective when given 5 days before training. The effectiveness of all peptides to attenuate puromycin-induced amnesia decreased as the interval between training and peptide treatment increased, indicating that the peptides influence memory processes, rather than general arousal. Z-Pro-Lys-Gly-NH2 was active at 24h after training, when the other peptides were no longer effective. Although it seems clear that neurohypophyseal hormones per se can attenuate puromycin-induced amnesia, these results are in line with the possibility that some portion of hormone action may be mediated via formation of longer-lived hormone fragments in the CNS.
 ...
PMID:Time-dependency of neurohypophyseal peptide attenuation of puromycin amnesia in mice. 719 22

In the proposed biologically active conformation of vasopressin at its antidiuretic receptor, the side-chain carboxamide moiety of the 5-position asparaginyl residue has been suggested to be an active element for the initiation of the antidiuretic response. [5-Aspartic acid] arginine vasopressin, the analog in which the -NH2 portion of the primary amide has been replaced by an -OH group, has been synthesized and tested for some of the pharmacological activities of vasopressin. The partially protected nonapeptide intermediate was assembled bidirectionally on a poly-N-acrylylpyrrolidine resin. The 6-position cysteinyl residue was attached to the resin via its side-chain through an S-carbamoyl linkage. First the COOH-terminus was extended by coupling with Pro-Arg(Tos)-Gly-NH2, then the NH2-terminus was extended in a stepwise manner. [5-Aspartic acid] arginine vasopressin was found to possess 86.5 +/- 4.8 units/mg of antidiuretic potency, 17% of the parent hormone. In addition, the analog possesses rat pressor and rat uterotonic potencies of 6.93 +/- 0.15 and 0.38 +/- 0.03 units/mg, respectively. This result suggests that a carboxylic acid moiety on the 5-position aspartyl residue retains sufficient steric features and hydrophilicity in common with the carboxamide moiety present in the hormone to substitute for it as an active element at the antidiuretic receptor.
 ...
PMID:Bidirectional synthesis of [5-aspartic acid] arginine vasopressin on poly-N-acrylylpyrrolidine resin. 721 12

The effect of vasopressin analogues on short-term memory was tested in the 12-arm radical maze. After the first 6 choices rat (n = 16) were removed from the apparatus and allowed to complete the remaining 6 choices 20 min later. Whereas desgly-NH2-VP, AVP, dAVP and dDAVP (3.0 mu/kg) administered 40 min before or immediately after the first 6 choices did not change the incidence of errors in the second series of choices (2.0 errors under control conditions), similarly applied dDAVP deteriorated the rat's performance almost to the chance level of 3 errors. The significance of short-term memory tests for assessing the mnestic role of peptide hormones is stressed.
 ...
PMID:Vasopressin analogues and spatial short-term memory in rats. 723 29


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