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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental conditions and parameters involved in high performance liquid chromatography (HPLC) separations of the peptide hormone oxytocin and seven of its diastereoisomers, namely [1-hemi-D-cystine]-, [2-D-tyrosine]-, [4-D-glutamine]-, [5-D-asparagine]-, [6-hemi-D-cystine-], [7-D-proline]-, and [8-D-leucine]-oxytocin, on reverse phase columns were investigated. The effects of solvent, pH, and salt concentration were studied. Using the solvent systems 10% tetrahydrofuran-ammonium acetate buffer or 18% acetonitrile-ammonium acetate buffer and the muBondapak C18 support, oxytocin was separated from each of its diastereoisomers under all conditions studied, but the order of elution of diastereoisomers was highly dependent on solvent and to a lesser extent on pH. Separations of the hormone and its diastereoisomers on reverse phase HPLC and on classical partition chromatography on Sephadex G-25 were compared. The results are discussed in terms of the interactions of the solute with the reverse phase column and the solvent system. Implications of these findings in terms of the different solution conformations of the peptides are discussed.
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PMID:The separation of peptide hormone diastereoisomers by reverse phase high pressure liquid chromatography. Factors affecting separation of oxytocin and its diastereoisomers--structural implications. 3 28

The specific binding of [125I]LH-RH to isolated plasma membranes of rat pituitaries was investigated. The binding process was found to be highly specific, temperature-dependent and saturable. The dissociation constant as caluclated by three different methods was approximately 1.3 . 10(-8) M, indicating a single type of binding sites. Maximal binding capacity was 1 . 10(-12 moles/mg protein (= 2 ng LH-RH/pituitary gland), and the number of binding sites was calculated to be 6 . 10(11) per mg membrane protein (=1 . 10(10) binding sites/pituitary gland). When diluted with ice-cold buffer the dissociation of specifically bound LH-RH occurred very rapidly (half-life 3.17 min) with a rate constant of 0.219 min-1. The dissociation process followed first-order kinetics. Specificity of binding was demonstrated by dose-dependent competition of unlabelled LH-RH, the highly potent analogue D-glutamine-(cyclohexyl)6-LH-RH-nonapeptide-ethylamide and the fragment of an analogue (6-D-Ser(TBu))-LH-RH-(3-9)-heptapeptide-ethylamide with the binding [125I]LH-RH, while angiotensin I, II, oxytocin and bacitracin did not compete. The affinities of LH-RH and the analogue to the binding sites of the pituitary plasma membranes were not consistent with the respective biological activities.
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PMID:Interaction of [125I]LH-RH and other oligopeptides with plasma membranes of rat anterior pituitaries. 22 10

[1-Deaminopenicillamine,4-threonine]oxytocin was prepared in duplicate from S-benzyl-3-mercapto-3,3-dimethylpropanoyl-Tyr(Bzl)-Ile-Thr(Bzl)-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 (I) by removal of the Bzl-protecting groups with Na-NH3, followed by cyclization of the resulting disulfhydryl compound with K3Fo(CN)6. The analogue was purified by desalting on Sephadex G-15 in 50% acetic acid and gel filtration of Sephadex G-15. The protected peptide I was synthesized (a) by the solid-phase method and (b) by a combination of solid-phase synthesis and an [8 + 1] coupling in solution. The analogue has no detectable agonist activity in rat vasopressor or isolated rat uterus assays. It has an antivasopressor pA2 of 6.67 +/- 0.09. It is a potent inhibitor of the in vitro oxytocic response to oxytocin and has a pA2 value of 7.46 +/- 0.04. (Material from the repeat synthesis has a pA2 value of 7.59 +/- 0.08.) Thus the substitution of threonine for glutamine in the antagonist [1-deaminopenicilliamine]oxytocin (pA2, 7.14 +/- 0.05) has effected a twofold increase in inhibitory potency. [1-deaminopenicillamine,4-threonine]oxytocin is one of the most potent inhibitors of oxytocin known to date.
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PMID:[1-Deaminopenicillamine,4-threonine]oxytocin, a potent inhibitor of oxytocin. 62 12

1 Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions.2 Glycine and the straight-chain L-alpha-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The omega-amino acids gamma-aminobutyric acid (GABA) and delta-aminovaleric, and the alpha,omega-diamino acids L-alpha,beta-diaminopropionic and L-alpha,gamma-diaminobutyric were active, whereas others of similar chain-length such as beta-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity.3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful.4 When some of the acids that were spasmogenic at 2 to 10 mM were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations.5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.
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PMID:Spasmogenic and potentiating actions of some amino acids on the guinea-pig myometrium. 92 51

Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the "oil-bath" technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the peristence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these "rapidly inactivated" analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.
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PMID:Modes of inactivation of neurohypophysial hormones: significance of plasma disappearance rate for their physiological responses. 105 86

Synthesis and biological properties are reported for some analogs of oxytocin with replacements of the isoleucine residue in position 3, i.e., (3-proline)oxytocin and(3-D-alanine)oxytocin, and the glutamine residue in position 4, i.e., (4-D-alanine)-oxytocin and (4-D-leucin)oxytocin. (3-Proline)oxytocin exhibited smaller than0.02 U/MG oxytocic activity, 0.005 plus or minus smaller than 0.001 U/mg rat pressor activity and 0.003 plus or minus 0.0001 U/mg antidiuretic activity. (3-D-Alanine)oxytocin had no agonistic activity in the bioassays tested except for the rat antidiuretic assay (smaller than 0.0005 U/mg). The 4-D-alanine analog showed 0.05 plus or minus 0.003 U/mg oxytocic activity, 0.07 plus or minus 0.01 U/mg avian vasodepressor activity, and smaller than 0.001 U/mg rat antidiuretic activity. (4-D-Leucine)oxytocin possessed 0.001 plus or minus U/mg rat pressor activity, and showed slight inhibitory properties in the oxytocic and avian vasodepressor assays, inhibiting the oxytocin response in the latter assay by about 60% at a girnibe-to-analog ratio of 1:5000. The activity profiles of the analogs are compared to that of oxytocin and are discussed on the basis of the proposed solution conformation of oxytocin.
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PMID:Oxytocin analogs with substitutions in postions 3 and 4. 114 Aug 89

The substitution of the 4-glutamine of oxytocin by a lipophilic aliphatic amino acid leucine yields [4-Leu] oxytocin which possesses natriuretic-diuretic anti-arginine-vasopressin (anti-ADH) activities. Alkyl substitutions of the beta-carbon of the 1 half-cystine of oxytocin yield a series of antioxytocin analogs which inhibit the uterotonic response to oxytocin. In this paper, the results of our further investigations on the molecular requirements for natriuretic, anti-ADH and antioxytocic activities of these peptides are reported. A total of 12 analogs of oxytocin and lysine-vasopressin (LVP) with leucine and/or beta-carbon alkyl substitutions were studied. Our findings reveal that the effect of 4-leucine substitution may not be to enhance the natriuretic activity but rather to abolish the antidiuretic activity of oxytocin. The lack of antidiuretic activity of these 4-leucine analogs makes it possible to unmask the intrinsic natriuretic activity of these peptides at the high dose level. Structure-activity correlations suggest that the oxytocin molecule may be the optimal requirement for natriuretic activity of these peptides. Substitution of 4-glutamine by lipophilic aromatic phenylalanine yields [4-Phe] oxytocin which possesses anti-ADH activity with little or no natriuretic activity. The "hybrid" antioxytocin and anti-ADH molecules, beta-carbon alkyl and 4-leucine substituted analogs did not possess enhanced antihormone activity. Although they had antioxytocic and antipressor activities, they were less potent than their respective singly alkyl substituted analogs. Furthermore, they had no demonstrable anti-ADH activity. The single alkyl substituted oxytocin and LVP also had no anti-ADH activity. It therefore appears that beta-carbon alkyl substitution had different effects on activities depending on the morphological features and the functions of the target cell. In target cells of contractile smooth muscles (uterus and vascular), the alkyl substituted analogs had no intrinsic activity but retained a relatively high receptor affinity to become effective antagonists to the natural hormone. On the other hand, in target cells of the renal tubule which are noncontractile epithelial cells, both intrinsic activity and receptor affinity were reduced or abolished. Thus none of these alkyl substituted analogs possessed more than very slight antidiuretic activity, and none had any natriuretic or anti-ADH activity.
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PMID:An investigation of the natriuretic, antidiuretic and oxytocic actions of neurohypophysial hormones and related peptides: delineation of separate mechanisms of action and assessment of molecular requirements. 126 21

Solution methods, using N-hydroxysuccinimide esters, were used to synthesize [Glu(NHNH2)4] oxytocin and [Glu(NHNH2)4, Lys8] vasopressin. In these analogs of neurohypophyseal hormones, the side-chain carboxamide function of a glutamine residue is formally replaced by a hydrazide group at position 4. The hormone analogs were assayed for uterototonic activity, milk ejection activity, antidiuretic activity, and rat pressor activity. The specific biological activities of the oxytocin and vasopressin analogs were decreased compared to the respective parent hormones in all assay systems.
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PMID:Synthesis and biological activities of oxytocin and lysine vasopressin analogs containing glutamic acid gamma-hydrazide in position 4. 261 36

The substitution of glutamine by threonine in position 4 of oxytocin, deamino-oxytocin, deamino-1-carba-oxytocin, and deamino-6-carba-oxytocin was found to increase the elimination rate of all analogs examined from the uterine receptor compartment in rat. However, this substitution was without any effect on the time course of uterotonic response in the case of vasotocin and deamino-vasotocin. These results suggest that the topological relationships of the 4 and 8 positions may show an important effect on elimination rate of oxytocin and vasotocin analogs from the rat uterine compartment.
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PMID:Effect of threonine in position 4 in oxytocin and vasotocin analogs on the time course of uterotonic response. 311 17

Preliminary observations [Sykes & Lowry (1980) J. Endocrinol. 85, 42P-43P] had suggested that the major hypothalamic somatoliberin (growth-hormone-releasing factor) was a larger peptide than the other characterized hypothalamic factors, with an elution position on Sephadex G-50 between those of neurophysin and corticotropin. The present paper reports the isolation and preliminary characterization of pig hypothalamic somatoliberin. Acid extracts of pig stalk median eminence were purified by gel filtration and preparative and analytical high-pressure liquid chromatography to yield a preparation that was specific in the release of somatotropin (growth hormone) in vitro, giving a steep dose--response curve at doses in the range 0.20-3.0 ng. Amino acid analysis revealed a non-cysteine-containing peptide with a high number of glutamate (or glutamine) and aspartate (or asparagine) residues. The peptide had about 56-57 amino acid residues and an apparent molecular weight of 6400, in keeping with its elution position on a column of Sephadex G-50.
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PMID:Purification of a high-molecular-weight somatoliberin (growth-hormone-releasing factor) from pig hypothalami. 640 74


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