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)

The structural interdependence between neurophysin (NP) self-association and ligand binding surfaces has been studied by analytical affinity chromatography of several NP sequence variants and derivatives on Met-Tyr-Phe-aminobutyl-agarose and bovine NP-II Sepharose. Elutions of radiolabeled NP's from both matrices show that hybrid dimers can form between major bovine NP's (I and II, or VLDV- and MSEL-NP's, respectively), as well as between human and bovine NP's, with affinities close to that for homologous dimer formation. Such evidence supports the view that the region of NP involved in NP-NP contact is composed primarily of conserved structural elements of the protein. NP antibodies which recognize surfaces close to or in the NP-NP contact region have been detected by their effects on bovine NP-II elution on NP-II Sepharose. Elutions of [3-nitro-Tyr 49] BNP-II from Met-Tyr-Phe-aminobutyl-agarose showed that nitration has little effect on the chromatographic properties of NP-II. This evidence substantiates previous arguments (Angal, S. & Chaiken, I.M. (1982) Biochemistry 21, 1574-1580) that the chromatographic behavior of native NP's on the affinity matrices is an expression of the interdependence of NP self-association and ligand binding surfaces and not due to bivalent peptide binding by NP monomer. The affinity chromatographic properties of NP derivatives, including bovine NP-II photolabeled in the ligand binding site and tryptic fragments of bovine NP-I (NP-I-(9-93) and [des 19-20] NP-I-(9-93)), support the view that the surfaces for ligand binding and NP-NP contact are conformationally linked. The data argue that conformational changes that ensue upon noncovalent ligand binding and lead to enhanced NP self-association cannot occur favorably with the protein modified by either covalent ligand attachment or limited amino-terminal proteolysis.
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PMID:Cooperative interactions in neurophysin-neuropeptide hormone complexes. Analytical affinity chromatography of native and covalently-modified neurophysins. 650 Aug 6

Two human neurophysins have been purified from acetone-desiccated posterior pituitaries by acidic extraction, molecular sieving, and ion-exchange chromatography. The complete amino acid sequence of each protein has been determined by using a sequencer and characterizing two sets of overlapping enzymic peptides. The two neurophysins belong to two structural families previously defined as MSEL- and VLDV-neurophysins according to the nature of the residues in positions 2, 3, 6, and 7. (MSEL-neurophysins contain methionine-2, serine-3, glutamic acid-6, and leucine-7; VLDV-neurophysins contain valine-2, leucine-3, aspartic acid-6, and valine-7.) Human MSEL-neurophysin has only 93 residues instead of 95 usually found in MSEL-neurophysins from other mammalian species, probably because of a deletion of amino acids 91 and 92. Compared with bovine MSEL-neurophysin, nine variations (seven substitutions and two deletions) are observed. Human VLDV-neurophysin has 93 residues, as do the other mammalian VLDV-neurophysins. There are 11 substitutions when the comparison is made with bovine VLDV-neurophysin. Between the two human neurophysins, there are 26 variations. However, the central parts of the proteins (residues 10-70) are nearly identical. Furthermore, in this region identical substitutions are found in positions 29 and 60 of both neurophysins, suggesting either a single exon or some relationship between the two corresponding genes.
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PMID:Identification of human neurophysins: complete amino acid sequences of MSEL- and VLDV-neurophysins. 657 52

The distribution of proenkephalin and [Met]enkephalin immunoreactivities in the bovine hypothalamo-neurohypophyseal system was studied by use of specific antisera. Proenkephalin and [Met]enkephalin immunoreactivities were found in magnocellular neuronal cell bodies in the dorsal part of the supraoptic nuclei and in the peripheral part of the paraventricular nuclei. A densely staining network of nerve terminals was found in the external part of the median eminence and in the posterior hypophysis. This general distribution is identical to that of the neurohypophyseal hormone oxytocin. The precise localization of proenkephalin and [Met]enkephalin immunoreactivities was compared to the distribution of oxytocin and vasopressin in serial 5-micron sections through the magnocellular nuclei. Oxytocin immunoreactivity was nearly always present in cells that were stained with proenkephalin and [Met]enkephalin antisera. The vasopressin-immunoreactive cells were never stained with either the proenkephalin or the [Met]enkephalin antisera.
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PMID:Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons. 657 80

Analysis of peptides by reverse-phase high-pressure liquid chromatography would be simplified if retention times could be predicted by summing the contribution to retention of each of the peptide's amino acid side chains. This paper describes the derivation of values ("retention coefficients") that represent the contribution to retention of each of the common amino acids and end groups. Peptide retention times were determined on a Bio-Rad "ODS" column at room temperature with a linear gradient from 0.1 M NaclO(4), pH 7.4 or 2.1, at 0 min to 60% acetonitrile/0.1 M NaclO(4) at 80 min. The NaclO(4), a chaotropic agent, was added to improve peak shape and to minimize conformational effects. Retention coefficients for the amino acids were computed by using a Hewlett-Packard 9815A calculator programmed to change the retention coefficients for all amino acids sequentially to obtain a maximum correlation between actual and predicted retention times. Correlations of 0.999 at pH 7.4 and 0.997 at pH 2.1 were obtained for 25 peptides including glucagon, oxytocin, [Met]enkephalin, neurotensin, and somatostatin. This high degree of correlation suggests that, for peptides containing up to 20 residues, retention is primarily due to partition processes that involve all the residues. Although steric or conformational factors do have some effect on retention, the data suggest that under the above chromatographic conditions the retention of peptides containing up to 20 residues can be predicted solely on the basis of their amino acid composition. This possibility was tested by using data taken from the literature.
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PMID:Prediction of peptide retention times in high-pressure liquid chromatography on the basis of amino acid composition. 692 13

Localization of enkephalins and opiate binding sites in the central nervous system of rats has been reported by several authors. These studies did not reveal an extensive enkephalinergic system in the hypothalamo-hypophyseal axis of rats. The present paper reports on an extensive enkephalinergic system in the cat hypothalamo-hypophyseal system. Sections of paraformaldehyde fixed cat hypothalami were incubated with anti-methionine enkephalin serum, anti-vasopressin serum, and anti-oxytocin serum. Immunohistochemical localization of methionine enkephalin fibers and terminals in the median eminence, hypophyseal stalk, and pars nervosa was similar, but not identical to the distribution of vasopressin and oxytocin in these structures. Neuronal perikarya localized with the three antisera in the nucleus supraopticus and nucleus paraventricularis were of a similar size and morphology. In cats treated with colchicine prior to sacrifice, the anti-methionine enkephalin serum revealed a group of periventricular cell bodies. Cell bodies were not localized in this area with anti-vasopressin or anti-oxytocin sera. The functional significance of such an extensive enkephalinergic system in the cat hypothalamo-hypophyseal axis is discussed.
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PMID:Relationship between enkephalinergic neurons and the vasopressin-oxytocin neuroendocrine system of the cat: an immunohistochemical study. 699 53

Evidence is accumulating that opiates inhibit the release of oxytocin and vasopressin by acting on nerve terminals in the neurohypophysis. Extracts of neurohypophysis have been shown to contain substantial amounts of Met- and Leu-enkephalin, and Leu-enkephalin-immunoreactive (IR) nerve fibres originating in the magnocellular hypothalamic nuclei have been described in the neural lobe, where the two hormones are secreted. We have compared the distribution of oxytocin, vasopressin and enkephalin immunoreactivity (IR) in the neurohypophysis of the rat, and report here that Met-enkephalin-IR is invariably associated with nerve terminals that contain oxytocin-IR whereas the terminals that contain vasopressin-IR often, but not invariably, are Leu-enkephalin immunoreactive.
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PMID:Enkephalins co-exist with oxytocin and vasopressin in nerve terminals of rat neurohypophysis. 700 86

The chemical structure of the hormone binding region of the neurophysins has been investigated by photoaffinity labeling with the photolabile tripeptide, L-[methyl-3H]Met-L-Tyr-p-azido-L-Phe amide. Photolysis of the photoaffinity tripeptide in the presence of bovine neurophysin I and II and a human neurophysin II led to approximately equal extents of covalent incorporation of radioactivity into protein. Photolabeled bovine neurophysin II was fractionated into binding site derivatized protein and nonbinding site derivatized protein by affinity chromatography, with results of amino acid and radiolabel analysis of the hormone binding site blocked protein indicating that 1 mol of tripeptide was covalently incorporated/mol of protein. Tyrosine 49 was the only protein amino acid modified in the binding site photolabeling reaction as assessed by peptide mapping of the performic acid oxidized and trypsin-digested photolabeled protein using reverse phase high performance liquid chromatography. Modification of the single neurophysin tyrosine also was found by amino acid analysis of performic acid oxidized photolabeled bovine neurophysin II. The covalent bond formed in neurophysin upon photolysis was cleaved by either exhaustive acid hydrolysis or reduction-carboxymethylation without loss of the protein amino acid residues and by performic acid oxidation with loss of both protein and tripeptide tyrosine residues. These overall data indicate that tyrosine 49 is the probable site for specific covalent attachment of the photoaffinity tripeptide. Assuming that the tripeptide binding site is the high affinity hormone binding site reported for the neurophysins, this conclusion argues that tyrosine 49 is close to or within this site.
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PMID:Photoaffinity labeling of the hormone binding site of neurophysin. 706 22

The reciprocal modulation of neurophysin self-association and noncovalent peptide--protein interaction between neurophysin and the hormones oxytocin and vasopressin has been assessed by quantitative affinity chromatography. Competitive elutions of radiolabeled bovine neurophysin II (NPII) from the affinity matrices Met-Tyr-Phe-omega-(amino-hexyl)- [and (aminobutyl)-] agarose were performed with increasing concentrations of either of the soluble ligands oxytocin or lysine-vasopressin. Also, the dependence of NPII retardation by the same adsorbents on the concentration of applied protein was investigated in the absence of soluble ligand. The affinity constant of NPII for the immobilized peptide increased markedly with increasing amounts of applied protein and with the addition of small amounts of soluble ligand, the latter being more pronounced at higher protein concentrations. The affinity constant of the protein for the soluble ligand showed a smaller increase. The variation of l/(V - V0) (where V = the NPII elution volume and V0 = the elution volume of noninteracting control protein) with soluble ligand concentration was linear except near [ligand] = 0. The quantitative affinity chromatographic results on the tripeptidyl affinity columns are consistent with the view that NPII exists in a monomer in equilibrium dimer equilibrium, with the dimer exhibiting a stronger interaction with both neuropeptide and tripeptide analogues. The data also indicate that the self-associated protein dimer itself exhibits cooperativity, that is, stronger binding of the immobilized ligand at one site when a second site is occupied with a molecule of the soluble ligand than when no soluble ligand is bound. The deduction from the above of ligand-induced dimerization is evident also in the increased retardation of NPII on neurophysin--Sepharose when the eluting buffer contains soluble peptide hormone.
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PMID:Interdependence of neurophysin self-association and neuropeptide hormone binding as expressed by quantitative affinity chromatography. 708 36

Limited tryptic fragmentation of disulfide-intact bovine neurophysins I and II (NP-I and -II, respectively) has been found to cause selective disruption of both hormone binding and neurophysin self-association. Loss of binding interactions, measured as a loss of ability to stimulate retardation of 125I-labeled neurophysin on Met-Tyr-Phe-amino-butylaminoagarose, is complete within 3 h at 37 degrees C. Reverse-phase high-performance liquid chromatography (HPLC) analysis of tryptic digests of neurophysin I allows detection of two major protein products and the peptide fragment 1-8. Release of the latter N-terminal piece occurs at about the same rate as loss of binding interactions. Reverse-phase HPLC elution behavior before and after performic acid oxidation and amino acid composition of the protein products led to their identification as NP-I-(9-93) (the 9-93 sequence) and [des-19,20]NP-I-(9-93) (the 9-93 sequence with the dipeptide 19-20 missing) for the more rapidly and more slowly formed species, respectively. NP-I-(9-93), unlike intact neurophysin I, is not retarded strongly by either Met-Tyr-Phe-amino-butylaminoagarose or neurophysin II-Sepharose. In contrast, both NP-I-(9-93) and [des-19,20]NP-I-(9-93) are equally as effective as intact NP-I in binding neurophysin I antibodies. The role of amino-terminal residues in promoting hormone binding, self-association, and antigenic recognition interactions is considered.
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PMID:Effects of limited tryptic proteolysis of bovine neurophysins on molecular properties of hormone binding, self-association, and antigenicity. 715 May 67

Subcutaneous injections of 30 mg atropine into lactating cows induced a 20--40% decrease of free amino acid (AA) levels in arterial plasma. Minimum levels were observed after 30--50 min. The decline persisted for more than 6 h. The greatest fall in concentration was noted for tyrosine, methionine, lysine, arginine, phenylalanine and threonine. Arterial glucose levels remained unaffected. The effect of atropine on milk secretion was studied in 2 cows which were milked every hour with the aid of oxytocin. Maximal effects were observed after 3--4 h. They included reduction in concentration of casein and alpha-lactalbumin (alpha-la) and a decline in production of milk (20%), casein (35%), alpha-la (45%) and lactose (18%). Uptake by the lactating udder over a period of about 1 h after injection of atropine was studied in 2 cows. Mammary blood flow and glucose uptake remained unaffected. There was a positive correlation between arteriovenous differences of essential AA and arterial plasma concentrations. The uptake of essential AA decreased by approximately 50%. There was no evidence that atropine has a direct inhibiting effect on the udder. It is suggested that the decrease of alpha-la synthesis might induce an inhibition of lactose synthesis and milk production.
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PMID:Effect of atropine on plasma amino acid levels and milk secretion of cows. 719 9


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