Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Three neurophysins, proteins that bind the polypeptide hormones oxytocin and vasopressin, have been isolated from acetone-dried porcine posterior pituitary lobes. The proteins have been named porcine neurophysins-I, -II and -III in order of their electrophoretic mobilities at pH8.1. 2. Electrophoretic comparison of the purified proteins, which are homogeneous on starch-gel electrophoresis, with the soluble proteins of fresh porcine posterior pituitary lobes extracted in 0.1m-HCl and in buffer pH8.1 suggests that the isolated proteins are native to the fresh tissue. 3. Neurophysins-I and -II are present in similar amounts in the tissue, whereas neurophysin-III is present only in small quantities. Acetone-dried tissue also contains traces of other hormone-binding neurophysin components. 4. All the neurophysins can bind both oxytocin and [8-lysine]-vasopressin. 5. The apparent molecular weights of the neurophysins increase with increasing protein concentration as measured by equilibrium sedimentation in the ultracentrifuge. 6. Neurophysins-I and -III are of similar molecular dimensions, contain one residue of methionine per molecule and lack histidine. The minimum molecular weight of neurophysin-I obtained by amino acid analysis is 9360. Neurophysin-II is of larger molecular dimensions than neurophysins-I and -III and can be separated from these by gel filtration on Sephadex G-75. It contains no histidine or methionine, and its minimum molecular weight has been estimated as 14020 by amino acid analysis. 7. Each of the three neurophysins possesses N-terminal alanine. 8. The possible biological significance of the existence of several neurophysins within one species is discussed.
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PMID:The isolation of three neurophysins from porcine posterior pituitary lobes. 544 78

A sensitive and precise method for assaying the water permeability response evoked by neurohypophyseal hormones and their synthetic analogues on the isolated urinary bladder of the toad (Bufo marinus L.) is described. The method permits detection of 8-arginine-vasotocin at concentrations as low as 10(-12)M. This sensitivity, not achieved heretofore with this tissue, results largely from minimizing interference of inhibitory substances by means of an "in vitro circulation assembly." The precision of the method derives from a direct comparison between the cumulative dose-response curve of an agonist of unknown potency acting on one hemibladder and that of a reference compound acting on the contralateral hemibladder. Crystalline deamino-oxytocin is used as the reference standard in this assay. The intrinsic activity of 2-(O-methyltyrosine)-oxytocin, as defined by the maximal response, is 12% lower than that of deamino-oxytocin. All other hormonal peptides investigated have the same intrinsic activity as deamino-oxytocin, even 5-valine-oxytocin, in spite of its extremely low affinity. A comparison of the potencies of 8-arginine-vasotocin vs. 8-arginine-vasopressin, 8-ornithine-vasotocin vs. 8-ornithine-vasopressin, 8-alanine-oxytocin vs. 8-alanine-oxypressin, and deamino-8-alanine-oxytocin vs. deamino-8-alanine-oxypressin suggests that an isoleucine residue in position 3 imparts a higher specificity for binding of the hormonal peptide molecule to the bladder receptor than a phenylalanine residue in this locus.
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PMID:A sensitive hydroosmotic toad bladder assay. Affinity and intrinsic activity of neurohypophyseal peptides. 569 11

1. A thiol proteinase from human pituitaries was purified approximately 400 fold and shown to have different chromatographic properties from that of calf brain. Among substrates cleaved were myelin basic protein, histones, beta-lipotropin, neurophysin, and Substance P. 2. The enzyme showed properties associated with a cathepsin-B like enzyme: dependence on -SH groups, pH optimum of 6.5, inhibition by leupeptin and a synthetic analog, Boc-D-Phe-Pro-arginal, and cleavage of dipeptidyl arylamides with basic residues adjacent to or penultimate to the chromatographic grouping. 3. Membranes present in the P2 fraction of rat brain contained three or more enkephalinases when submitted to DEAE-cellulose chromatography. Further purification on an IgG-Sepharose affinity column prepared with antibody to lung angiotensin converting enzyme indicated the presence of dipeptidyl carboxypeptidase(s) with properties distinct from those of ACE. In addition, the DEAE-cellulose fractions contained various aminopeptidase activities when tested with Leu-Gly-Gly, Leu-Nap, and Ala-Ala-Nap as substrates.
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PMID:Peptide processing in the central nervous system. 625 8

A glycoprotein of neurohypophysial origin was found to have cofractionated with FSH prepared from pituitary glands of the green turtle, Chelonia mydas. Antiserum raised against this preparation contained high antibody titres and affinity for the neurohypophysial component and allowed development of a specific radioimmunoassay to monitor its purification and distribution in the brain. Immunocytochemistry revealed that the glycoprotein was concentrated in the pars nervosa and associated nerve tracts passing through the median eminence to the supraoptic and paraventricular nuclei; similar distributions were observed in turtles and rats. The antiserum to the turtle material bound radiolabelled rat vasopressin (VP)-neurophysin and precipitated precursors of this neurophysin, but it did not cross-react with rat oxytocin-neurophysin. An amino-terminal alanine was also consistent with the structure of rat VP-neurophysin, but the turtle molecule was larger than the corresponding rat molecule. Limited tryptic digests of the turtle glycoprotein contained two components, one of which bound to lysine VP. Both components contained carbohydrate, but only the one which bound to VP cross-reacted in a radioimmunoassay for rat VP-neurophysin. The apparent surge in plasma immuno-FSH at the time of oviposition previously described in the turtle probably represented release of a neurophysin-like 'carrier' molecule associated with secretion of the neurohypophysial hormone (e.g. arginine vasotocin; AVT) responsible for oviduct contractility. These data suggest that the neurohypophysial glycoprotein represents a partially processed AVT precursor and provide the first biochemical evidence of a mammalian-like biosynthetic pathway for neurohypophysial hormones in a non-mammalian species.
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PMID:Presence of a neurophysin-like precursor in the green turtle (Chelonia mydas). 643 86

Studies were carried out on the right auricle of the right atrium of two-day-old rats placed in a special chamber perfused with Ringer-Locke solution at room temperature. The contractions rate of the auricle was counted with the use of a stereomicroscope. The following amino acids dissolved in Ringer-Locke solution were tested: glycine, glutamic acid, serine, alanine, aspartic acid, gamma aminobutyric acid, leucine, and peptides: vasopressin and oxytocin. Glutamic acid in a concentration of 10(-1) mol/l induced a decrease in auricle contraction rate by 25%. Alanine in concentration 10(-2) mol/l induced a decrease by 22%. Leucine in concentration 10(-2) mol/l induced a decrease by 16% and in concentration ten times higher a decrease by 28%. The other tested amino acids, vasopressin and oxytocin in concentration used had no influence on the rate of contraction frequency of the isolated auricle.
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PMID:The influence of amino acids, vasopressin and oxytocin on spontaneous contraction of the right auricle of the right atrium of two-day-old rats in vitro. 654 86

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)
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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

17O was introduced into the respective alpha- and gamma-COOH groups of Boc-Gly and Boc-Glu by saponification of the corresponding O-methyl esters with 1N NaOH in H2 17O. Other 17O enriched Boc-amino acids were prepared by acid catalyzed exchange into the amino acid alpha-COOH group followed by t-butyloxycarbonylation with t-butyl S-4, 6-dimethylpyrimidin-2-ylthio carbonate. Final enrichment, by approximately three orders of magnitude over natural abundance, was 60-100% of the possible maximum. The synthesis of [17O]-Gly-Ala, [17O]-Gly-Leu and [17O]-Gly-Glu by DCC/HBT mediated coupling of Boc-Gly-[17O]-alpha-COOH with amino acid-O-t-butyl esters followed by deprotection with HCl/EtOAc proceeded without undue loss of the isotope. Boc-[17O]-Pro-Leu-Gly-NH2 was prepared by a similar procedure. [Tyr2-17O]-, [Pro7-17O]- and [Gly4-17O]-oxytocin were synthesized using solid phase support. 17O-chemical shifts of synthetic intermediates and of the final products were as expected for each functional group. Linewidth data correlate with the molecular weights of the compounds prepared.
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PMID:Labeling of amino acids and peptides with isotopic oxygen as followed by 17O-N.M.R. 734 24

1. Modulatory effects of the four molluscan neuroactive peptides. FMRFamide (Phe-Met-Arg-Phe-NH2), APGW-amide (Ala-Pro-Gly-Trp-NH2), oxytocin and [SER2]-Mytilus inhibitory peptide ([SER2]-MIP) (Gly-Ser-Pro-Met-Phe-Val-NH2) were examined on the inward current (Iin) caused by achatin-I (Gly-D-Phe-Ala-Asp), which has been isolated from the Achatina ganglia. 2. Two Achatina giant neurone types, v-RCDN (ventral-right cerebral distinct neurone) and PON (periodically oscillating neurone), were used. Achatin-I was applied locally to the neurone tested by brief pneumatic pressure ejection, and the other molluscan neuroactive peptides were perfused around the ganglia. 3. FMRFamide, perfused at 3 microM, suppressed markedly the Iin elicited by the achatin-I of both v-RCDN and PON. APGW-amide at 3 microM also suppressed the Iin of v-RCDN, but did not affect that of PON. Oxytocin at 1 microM suppressed the Iin of PON, but did not affect that of v-RCDN. [Ser2]-MIP at 3 microM did not affect the Iin of v-RCDN. 4. The dose-response curves of FMRFamide, APGW-amide and oxytocin, indicated that their respective suppressive effects on the Iin of achatin-I were dose-dependent, and that APGW-amide was slightly more potent than the other peptides. The dose (pressure duration)-response curves of achatin-I (1 kg/cm2, 10(-3) M, 5 min interval), obtained by varying the duration of the achatin-I pressure ejection, were measured in the presence and absence of each of the three peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppressing effects of neuroactive peptides on the inward current caused by achatin-I, an Achatina endogenous peptide. 754 26

In the ruminant ovary, synthesis and secretion of oxytocin begin in the granulosa cells of the preovulatory follicle and are markedly stimulated by the surge of LH and FSH. Luteinization of the granulosa cells results in a further increase in oxytocin gene expression, but translation of mRNA appears to be retarded because the peak concentration of luteal oxytocin occurs later than the maximal accumulation of the message. Several hormones have been shown to stimulate oxytocin secretion from granulosa and luteal cells in vivo or in vitro. However, the role of prostaglandin F2 alpha (PGF2 alpha) in regulating luteal oxytocin secretion has perhaps received more study than other hormones. The mechanism of action of PGF2 alpha has been shown to encompass a phosphoinositide cascade and activation of protein kinase C, events that are associated with luteal secretion of oxytocin. Protein kinase C phosphorylation of the actin-binding protein myristolated alanine-rich C kinase substrate (MARCKS) may be required for exocytosis of oxytocin.
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PMID:Dynamics of molecular mechanisms underlying ovarian oxytocin secretion. 762 28

Familial central diabetes insipidus is an autosomal dominant disease caused by a deficiency of arginine vasopressin (AVP). We previously reported three distinct mutations in the AVP gene in Japanese familial central diabetes insipidus pedigrees that result in a substitution of Ser for Gly57 in the neurophysin-II (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH-terminus of the signal peptide, and a deletion of Glu47 in the NPII moiety. In this study, we analyzed the AVP gene in two pedigrees by direct sequencing of the polymerase chain reaction-amplified DNA and found two novel mutations in exon 2, which encodes the central part of the NPII moiety of the precursor. The mutation in one pedigree was a C to A transition at nucleotide position 1891, which replaces Cys67 (TGC) with stop codon (TGA). As the premature termination eliminates part of the COOH domain of the NPII moiety and the glycoprotein moiety, the conformation of the truncated protein is likely to be markedly different from that of normal precursor. In another pedigree, a G to T transversion was detected at nucleotide position 1874, which substitutes polar Trp (TGG) for hydrophobic Gly62 (GGG). It is possible that mutated NPII molecules, as a consequence of a conformational change, cannot bind AVP or self-associate to form higher oligomer complexes. Interestingly, all mutations we have identified to date, with the exception of the signal peptide mutation, are located in exon 2, suggesting the importance of the highly conserved central part of the NPII molecules and/or the NPII moiety in the precursor for AVP synthesis.
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PMID:Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus. 771 10


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