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 effects of bPTH-(1-34), oxidized bPTH-(1-34),[Nle8,Nle18, Tyr34] bPTH-(1-34) amide, and oxidized [Nle8,Nle18,Tyr34]bPTH-(1-34)amide were tested in an in vitro rat uterine assay. When bPTH-(1-34) was treated with hydrogen peroxide (H2O2), the ability of this peptide to reduce oxytocin-stimulated uterine contraction in vitro was no longer evident. An analogue of bPTH-(1-34), in which the methionines at positions 8 and 18 were replaced with norleucine ([Nle8,Nle18,Tyr34]bPTH-(1-34)amide), was capable of reducing oxytocin-stimulated uterine contraction. However, when the [Nle8,Nle18,Tyr34]bPTH-(1-34)amide was oxidized, it retained the ability to reduce uterine contraction. Since we have previously shown that H2O2 oxidation affected only the methionines, these results suggest that the methionines are not necessary for the uterine activity of bPTH-(1-34). We have previously shown that oxidation of bPTH-(1-34) also destroys its blood vessel relaxing activity but has no effect in the rat or the Japanese quail hypercalcemic assays. These data combined with the results of the present studies suggest that the uterine and vascular smooth muscle relaxing properties of bPTH-(1-34) may require the same structural conformation and that this conformation is different from that required for the hypercalcemic action of the peptide.
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PMID:Uterine relaxing action of parathyroid hormone: effect of oxidation and methionine substitution. 670 44

Non-anaesthetized rats were used for studying the relationship between the amount of sodium excreted and structural modifications of oxytocin molecule. Any change performed in position 4 (i.e. the glutamine residue) resulted in a decrease of natriuretic activity as compared to that of oxytocin. The analogues with modifications in the amino-terminal part of the molecule (e.g. substitution of the amino group in position 1 by hydrogen, or of the disulfide bond by a thioether group) resulted in a higher natriuretic effect than oxytocin.
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PMID:Effect of some oxytocin analogues on natriuresis in rats. 696 12

[5-beta-Malamidic acid]oxytocin was synthesized to study the importance of the hydrogen bond between the C=O of Tyr2 and the peptide N-H of Asn5 for the stabilization of a biologically functional conformation of oxytocin. This analog lacks the peptide N-H at residue 5 required for the formation of a hydrogen bond with the C-O of Tyr2. [5-beta-Malamidic acid] oxytocin exhibited 45.1 +/- 2.5 U/mg and 65.6 +/- 5.9 U/mg of uterotonic activity, in vitro, in the absence and in the presence, respectively, of Mg2+, 147 +/- 14 U/mg of uterotonic activity in vivo, 203 +/- 13 U/mg of milk-ejecting activity, 0.37 +/- 0.03 U/mg of pressor activity and 0.32 +/- 0.29 U/mg of antidiuretic activity. It is concluded that devoid of the hydrogen bond under question, an oxytocin-like peptide can still assume the conformation needed to interact with the oxytocin receptors.
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PMID:Biofunctional evaluation of a hydrogen bond stabilizing the conformation in the cyclic part of oxytocin. 711 27

In a continued effort to determine the importance of the hydrogen bonds for stabilization of the biologically active conformation of oxytocin, deamino-[9-glycolicamide] oxytocin was synthesized in order to study, in this respect, the hydrogen bond between the peptide N--H of Gly9 and the C=0 of Cys6. In this analog the amide linkage between residues at positions 8 and 9 is replaced by an ester. Thus the residue at position 9 cannot be involved in hydrogen bond formation with the C=O of Cys6. Deamino-[9-glycolicamide] oxytocin exhibited 134 +/- 13 U/mg and 355 +/- 48 U/mg of uterotonic activity in absence and in presence, respectively, of Mg2+, 108 +/- 8 U/mg of milk-ejecting activity, 0.35 +/- 0.03 U/mg of pressor activity and 2.5 +/- 0.1 U/mg of antidiuretic activity. It is concluded that the hydrogen bond under question is not critical for the conformation required for biofunctional interaction of oxytocin with its receptors in the uterus, mammary gland and other target organs.
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PMID:Biofunctional evaluation of a hydrogen bond stabilizing the beta-turn in the acyclic part of oxytocin. 719 72

At 400 MHz the 1H chemical shifts, peptide NH-C alpha H coupling constants (JN alpha) and peptide hydrogen exchange rates of [Glu4] oxytocin in aqueous solution closely resemble those previously reported for oxytocin under comparable conditions, indicating that both the parent hormone and its analogue have similar conformations in this solvent. The hydrogen exchange data suggest a dynamic equilibrium between conformation(s) in which the peptide NH's of Asn5 and Cys6 are internally hydrogen bonded and conformation(s) in which these hydrogens are bonded to the solvent. [Glu4] oxytocin forms 1:1 complexes with lanthanide metal ions. The diamagnetic La3+ complex exhibits values of JN alpha very similar to those of the metal free hormone analogue, suggesting that coordination of the metal is accompanied by minimal perturbation of the peptide backbone. Specific average proton-metal distances estimated from Gd3+ induced paramagnetic relaxation effects indicate that the metal is probably coordinated to the Glu4 carboxyl group and the sidechain carbonyl of Asn5. Limiting shifts induced by binding of paramagnetic Yb3+ are also reported.
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PMID:H N.M.R. study of the conformation of [Glu4] oxytocin and its lanthanide complexes in aqueous solution. 722 92

The primary structure of an elephant neurophysin, homologous to vasopressin-associated neurophysins, is reported. The protein contains a Tyr for Asn substitution at position 75, a position in direct contact with residues 77 and 78 of the monomer-monomer interface. This Tyr residue therefore serves as a potential reporter of the path involved in the long-range linkage between peptide binding and dimerization in this system. NMR studies of the protein in unliganded and liganded states demonstrated normal dimerization properties and the expected increase in dimerization associated with binding peptide. In keeping with an elevated pKa of 11.1 assigned to Tyr-75 by UV spectrophotometric titration, the NMR signals from the 3,5 and 2,6 ring protons of Tyr-75 were shifted 0.3 and 0.2 ppm upfield, respectively, relative to their positions in small peptides, indicating significant shielding and/or hydrogen bonding. The Tyr-75 ring proton signals narrowed slightly, with no discernible change in chemical shift, on conversion from dimer to monomer in the unliganded state. Ring protons of Tyr-49, distant from the monomer-monomer interface, but adjacent to the peptide-binding site, were markedly perturbed by dimerization, in accord with their behavior in bovine neurophysins. The results suggest that the secondary and tertiary structure of the region 75-78 is largely unchanged by dimerization, and argue against an important role for this region in dimerization-mediated conformational changes that alter the binding site in the unliganded state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid sequence and properties of vasopressin-associated elephant neurophysin. 782 4

The hormonal precursor pro-ocytocin-neurophysin is activated by selective cleavage at Arg2-Ala13, producing mature ocytocin and neurophysin. To understand the cleavage mechanism better, and in particular the recognition of the cleavage site, it is necessary to characterize the three-dimensional structure of the precursor molecule. Here we combine a variety of experimental data with molecular modeling and dynamics calculations to derive possible precursor conformations. In the models obtained, the N-terminus of the precursor, corresponding to the ocytocin segment, is hydrogen bonded in a pocket of the neurophysin moiety in a similar manner to a crystallographically obtained non-covalent complex between the two molecules. The calculations suggest that although the ocytocin segment is relatively flexible, it adopts a stable, broad loop structure in the vicinity of the cleavage region, which may constitute the structural element recognized by the cleaving enzyme. The calculations also suggest a possible widening of the distance between the two neurophysin domains in the precursor relative to that in the non-covalent neurophysin-ocytocin complex.
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PMID:Structural modeling of the pro-ocytocin-neurophysin precursor. 986 10

An artificial polymeric receptor prepared by the epitope approach of molecular imprinting was shown to recognize the peptide hormone, oxytocin, in aqueous media. The proposed approach is based on using (as a template) a compound, whose structure represents a small exposed fragment of a larger molecule (as an epitope represents an antigen). A HPLC study has demonstrated the important role of ionic interactions and the N-terminal amino group of oxytocin and oxytocin-related peptides in the process of their recognition by the molecularly imprinted polymer in the aqueous-rich media. However, the specificity of the process is considered to be defined by hydrophobic interactions and hydrogen bonding. Moreover, it was shown that the selectivity of the molecularly imprinted polymer can be attenuated by water content, ionic strength and pH of the chromatographic mobile phase: depending on these factors the template, Tyr-Pro-Leu-Gly-NH2, or, for example, oxytocin, a larger peptide, which possesses the same three amino-acid C-terminal parts of the structure, can be preferentially retained by the molecularly imprinted polymer.
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PMID:Recognition of oxytocin and oxytocin-related peptides in aqueous media using a molecularly imprinted polymer synthesized by the epitope approach. 1098 43

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.
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PMID:L-cysteine and sodium hydrosulphide inhibit spontaneous contractility in isolated pregnant rat uterine strips in vitro. 1132 78

Oxytocin is a neurohypophyseal peptide hormone that induces labor and lactation in mammals. An inverse gamma-turn mimetic corresponding to the tripeptide Ile-Val-Asn has been synthesized and incorporated instead of residues 3-5 of oxytocin to probe the hypothesis that a gamma-turn involving these residues is found in the receptor bound conformation of oxytocin. In the turn mimetic, residues i and i + 1 are connected by a psi[CH(2)O] isostere while a covalent methylene bridge replaces the hydrogen bond that is often found between residues i and i + 2 in gamma-turns. The turn mimetic was assembled from three types of building blocks: an azido epoxide, an alpha-bromo acid, and a protected beta-amino alcohol. The oxytocin analogue did not induce contractions of the uterus nor did it inhibit oxytocin-induced contractions. It is suggested that the loss of bioactivity is mainly due to the presence of a psi[CH(2)O] isostere instead of an amide bond between residues i and i + 1 in the turn mimetic.
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PMID:Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn. 1203 59


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