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)

The influence of a i.v. injection of 2 I.U. of synthetic oxytocin (Oxy, Syntocinon) on plasma cortisol has been tested in 6 normal volunteers (age 22 to 33) and compared to a similar saline injection in a blind, cross-over design. Before injection basal cortisol is similar in Oxy (12.1 +/- 2.3 micrograms/100 ml M +/- Se) and saline (11.7 +/- 3.5) groups; in the Oxy group a significant (2 p less than 0.01) decrease of cortisol was noticed from the 45th min until the end of the test (120 min): the last mean level being 5.2 +/- 0.9 in the Oxy group compared to 12.9 +/- 1.8 in the saline group (2 p less than 0.005). Although the mechanism of action of Oxy on cortisol plasma levels remains to be investigated our results are in agreement with a proper action of Oxy and vasopressin at the level of the corticotroph cells or with a proper action of Oxy or of one of its metabolite (Pro-Leu-Gly-NH2 for example) on proopiomelanocorticotropic function.
 ...
PMID:[Intravenous injection of synthetic oxytocin induces a decrease of cortisol plasma level in normal man]. 645 79

As part of a program in which we are attempting (a) to delineate the structural features at positions 1-9 in our previously reported antidiuretic antagonists required for antidiuretic antagonism and (b) to obtain analogues with enhanced antiantidiuretic potency and/or selectivity, we have synthesized 14 new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D-phenylalanine,4-valine]arginine-vasopressin [d-(CH2)5-D-Phe2VAVP), in which the valine residue at position 4 was replaced by the following L-amino acids and glycine: Ile, Abu, Thr, Ala, Gln, Lys, Cha, Nle, Nva, Phe, Leu, Gly, Tyr, and Pro. These analogues are 1, d-(CH2)5-D-Phe2,Ile4AVP; 2, d(CH2)5-D-Phe2,Abu4AVP; 3, d(CH2)5-D-Phe2,Thr4AVP; 4, d(CH2)5-D-Phe2,Ala4AVP;5, d(CH2)5-D-Phe2AVP; 6, d(CH2)5-D-Phe2,Lys4AVP; 7, d(CH2)5-D-Phe2,Cha4AVP; 8, d(CH2)5-D-Phe2,Nle4AVP; 9, d(CH2)5-D-Phe2,Nva4AVP; 10, d(CH2)5-D-Phe2,Phe4AVP; 11, d(CH2)5-D-Phe2,Leu4AVP; 12, d(CH2)5-D-Phe2,Gly4AVP; 13, d(CH2)5-D-Phe2,Tyr4AVP; 14, d(CH2)5-D-Phe2,Pro4AVP. The protected intermediates required for the synthesis of all of these peptides were prepared by the solid-phase method and cleaved from the resin by ammonolysis. Following deblocking with Na in NH3 and oxidizing with K3[Fe(CN)6], each peptide was purified on Sephadex G-15 in a two-step procedure using 50% HOAc and 0.2 M HOAc as eluants. Analogues 1-14 were tested for agonistic and antagonistic activities by antidiuretic, vasopressor, and oxytocic assays in rats. Analogues 1, 2, and 4-6 exhibit no detectable antidiuretic agonistic activity. All analogues, with the exception of the Pro4-containing analogue, are antidiuretic antagonists. Their antiantidiuretic pA2 values are as follows: 1, 8.24 +/- 0.08; 2, 7.96 +/- 0.07; 3, 7.62 +/- 0.09; 4, 7.52 +/- 0.03; 5, 7.21 +/- 0.07; 6, 7.22 +/- 0.12; 7, 7.19 +/- 0.08; 8, 7.12 +/- 0.09; 9, 6.99 +/- 0.06; 10, 6.07 +/- 0.11; 11, 6.07 +/- 0.11; 12, 5.85 +/- 0.05; 13, approximately 5.57; 14, a weak agonist (0.004 U/mg). Analogues 1-14 also antagonize the vascular responses to arginine-vasopressin (AVP) and the in vitro oxytocic responses to oxytocin. Analogues 1, 2, 3, and 5 have also been shown to antagonize the in vivo oxytocic responses to oxytocin. Five of these analogues (1, 2, 3, 6, and 7) exhibit enhanced antiantidiuretic/antivasopressor selectivity. d(CH2)5-D-Phe2,Lys4AVP and other position-4 analogues with side-chain functional groups may be useful covalent ligands with which to probe the structural characteristics of AVP renal and vascular receptors. With an antiantidiuretic "effective dose" of 0.46 +/- 0.07 nmol/kg and a pA2 value of 8.24 +/- 0.08, d(CH2)5-D-Phe2,Ile4AVP (1) appears to be the most potent antidiuretic antagonist reported to date.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Potent antagonists of the antidiuretic responses to arginine-vasopressin based on modifications of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D- phenylalanine,4-valine]arginine-vasopressin at position 4. 663 16

The nonapeptide hormone oxytocin-like arginine-vasopressin (AVP) is synthesized as part of a larger precursor polypeptide. The precursor also includes the neurophysin molecule with which the hormone is associated in the neurosecretory granules of the hypothalamo-pituitary tract. A protein of molecular weight (Mr) approximately 20,000 has been isolated from supraoptic nuclei of rat hypothalami which, after tryptic cleavage, released a neurophysin-like molecule of Mr approximately 10,000 and an oligopeptide related to oxytocin. This result was complemented by in vitro translation of bovine hypothalamic mRNA. Among the primary translation products a single polypeptide of Mr approximately 16,500 was shown to contain antigenic determinants recognized by specific antisera against bovine neurophysin I and oxytocin. Here we report the amino acid sequence of the bovine oxytocin-neurophysin I (OT-NpI) precursor which was derived from sequence analysis of the cloned cDNA. As is the case for the bovine arginine-vasopressin-neurophysin II (AVP-NpII) precursor, the signal sequence of the OT-NpI precursor is immediately followed by the nonapeptide hormone which is connected to neurophysin I by a Gly-Lys-Arg sequence. A striking feature of the nucleic acid sequence is the 197-nucleotide long perfect homology with the AVP-NpII precursor mRNA sequence encoding the conserved middle part of neurophysins I and II.
 ...
PMID:Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor cDNA. 668 26

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

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

A post-proline cleaving enzyme [post-proline endopeptidase: EC 3.4.21.26] was purified from lamb brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and Sephadex G-150. The purified enzyme appeared homogeneous on disc gel and sodium dodecyl sulfate (SDS) gel electrophoreses. The enzyme was most active at pH 7.0 with carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap) as a substrate and catalyzed the hydrolysis of oxytocin, vasopressin, thyrotropin releasing hormone (TRH), substance P, luteinizing hormone releasing hormone (LH-RH), and angiotensin at the carboxyl side of their proline residues, except for the Pro2-Lys3 bond in substance P. From the results of subsite mapping using synthetic peptides, five subsites, S3 to S2', for substrate interaction with the enzyme were deduced to be present, and high stereospecificity was observed at S2, S1, and S1'. The isoelectric point of the enzyme was at pH 4.9, and the molecular weights estimated by gel filtration and SDS gel electrophoresis were 74,000 and 77,000, respectively. The enzyme was markedly inhibited by diisopropylphosphoro fluoridate (DFP), carbobenzoxy-Gly-Pro-chloromethyl ketone (Z-Gly-Pro-CH2Cl), p-chloromercuribenzoate (PCMB), Hg2+, and Cu2+ ions. These enzymatic and protein chemical properties of post-proline cleaving enzyme from lamb brain closely resemble those of the lamb kidney enzyme, except for the molecular weight. In the present work, however, we decided that the molecular weight of the enzyme from lamb kidney was also 74,000, which is different from that reported previously (J. Biol. Chem. 251, 7593 (1976) but is in accord with the value of post-proline cleaving enzyme from lamb brain.
 ...
PMID:Post-proline cleaving enzyme from lamb brain. 702 30

Vasopressin (VP) neurons project to extrahypothalamic sites involved in pain perception, including the substantia gelatinosa of the spinal cord as well as the trigeminal and vagus nerves. Previous studies have reported antinociceptive activity following intracerebroventricular (ICV) or subcutaneous (SC) VP injections (16-100 microgram) on the tail-flick test while hyperalgesia has been observed in rats either genetically deficient in VP or treated with antisera to VP. The present study investigated whether nanogram (ng) doses of lysine-vasopressin (LVP) and a VP analogue with prolonged activity increased tail-flick latencies and flinch-jump thresholds following ICV or SC injections. LVP (150 and 500 ng, ICV) significantly increased tail-flick latencies while the analogue 1-deamino-(8-Lys-N epsilon-(Gly-Gly-Gly))-VP (500 ng, ICV) produced more powerful and prolonged analgesia. In contrast, latencies were not increased by SC injections of LVP (150-1500 ng). Further, flinch-jump thresholds were affected minimally by either ICV or SC LVP injections. These data suggest a role for VP in pain modulation and a central site of this action.
 ...
PMID:Central antinociceptive effects of lysine-vasopressin and an analogue. 713 29

Intracerebroventricular administration of fragments of [arginine8]-vasopressin (AVP) such as AVP1-6 and AVP7-9 attenuated the pressor response evoked by electrical stimulation of the mesencephalic reticular formation in urethane-anaesthetized rats. Oxytocin (OXT) and the fragment OXT7-9 were also active, although OXT1-6 did not affect the pressor response. These peptides did not influence the bradycardia accompanying the rise in blood pressure, nor the basal blood pressure. The inhibition of the pressor response was shown for OXT7-9 to be dose-dependent up to 25 ng. These data suggest that oxytocin, vasopressin and some neuropeptide fragments have an inhibitory role in the regulation of blood pressure. Both the covalent pressinoic ring structure and the C-terminal linear portion of vasopressin contain active sites, while the activity of oxytocin appears to be present in the C-terminal tripeptide Pro-Leu-Gly.
 ...
PMID:Inhibition of centrally-evoked pressor responses by neurohypophyseal peptides and their fragments. 715 15

[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


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