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

Mucosal acidification to pH 6.5 reduced by 88% the oxytocin- (2.2 x 10(-8) M) elicited increase of water permeability in frog urinary bladder. Mucosal alkalinization (pH 10.5) increased by as much as 200% the response to the same concentration of oxytocin. These effects were not observed when supramaximal concentrations of oxytocin were imployed. Similar changes were found when the serosal pH was modified. The hydrosmotic responses elicited by serosal hypertonicity or cyclic AMP plus theophylline were also affected by mucosal or serosal changes of the hydrogen in concentration, suggesting an effect at a post-cyclic AMP level. Important interactions were found between luminal pH and serosal hypertonicity when experimental conditions were employed similar to those observed in the collecting duct of mammalian nephron. Freeze-fracture studies showed that the number of intramembranous aggregates of particles induced by ADH in the luminal membrane was reduced by mucosal acidification and augmented by an increase in medium pH.
 ...
PMID:Influence of mucosal and serosal pH on antidiuretic action in frog urinary bladder. 4 16

This investigation was undertaken to evaluate the functional contribution of the peptide backbone of oxytocin in its interaction with receptor. Corey-Pauling-Koltun models of (Gly-7) deaminooxytocin, deaminotocinamide, and their respective retro-D-analogs built in any specific conformation (e.g., the Walter-Urry model for oxytocin) have a quai-equivalent topochemical arrangement of amino-acid side chains; however, the CO and NH elements of the peptide backbone of the retro-D-analog are reversed. The retro-D-analogs of deaminotocinamide and (Gly-7) deaminooxytocin (prepared using D-alle for L-Ile) and their respective N-formyl derivatives were assayed for uterotonic activity relative to related L-peptides. All retro-D-analogs (tested at concentrations ranging from 10-10 to 10-5 M) were devoid of angonistic (or antagonistic) activity in the isolated rat uterus, except for the retro-D-(D-alle-3, Gly-7) deaminooxytocinamine, which retains a terminal NH-2 group on the tail; the latter is a partial agonist with very low affinity. The results obtained with retro-D-analogs indicate that one or more of the elements of the peptide backbone of the tocinamide ring are essential for "occupation" and "activation" of uterine receptors. Oxytocin action may be the resultant of multiple hydrogen-bonding interactions between CO, NH, NH-2, and OH groups of the hormone with complementary groups on receptor, made possible by appropriate hydrophobic bonding.
 ...
PMID:Contribution of the peptide backbone to the action of oxytocin analogs. 16 58

A highly specific tritium labeled oxytocin (3H-OT) was synthesized utilizing the method of catalytic substitution of halogen for hydrogen. The specific activity of 3H-OT was 19 Ci/mM and the biologic activity was 350 U/mg, which was sufficient for the OT radioreceptor assay. The maximum % uptake of 3H-OT in the human myometrium was observed in 20,000 X g pellets under the optimal conditions of pH 7.4, at 20 degrees C and the incubation time of 90 min and it was augmented in the presence of Mn++. It was observed from the Scatchard plot, that the binding site of OT in the human myometrial specimens was a single type within the range of OT concentration of 0.4 nM to 1.6 nM. The dissociation constants (Kd) and the number of binding sites (NBS) showed a relative increase as gestation advance. The apparent Kd of term pregnancies was 1.25 X 10(-9) M regardless of the presence or absence of labor pains, while the NBS of term pregnancies with and without labor pain was 1.2 X 10(-12) and 4.7 X 10(-12) moles/mg, protein, respectively.
 ...
PMID:Study of oxytocin receptor in human myometrium using highly specific 3H-labeled oxytocin. 22 64

Proton magnetic resonance spectroscopy was used to monitor individual amino acid residues in bovine neurophysin, in the nonapeptide hormone oxytocin, and in the complex formed between them. For neurophysin I alone, a normal titration curve for the C-2 proton resonance of the lone histidine residue was obtained with an apparent ionization constant of 6.9 addition of oxytocin to a solution of neurophysin I at pH 6.5 resulted in several changes in the spectrum. The effect on the histidine C-2 proton resonance signal indicated a slow exchange process between two states, probably representing a conformational change in the protein. The apparent pK of the histidine residue in the hormonal complex was shifted to 6.7, indicating a slightly more positive (less electron dense) environment for the histidine residue. Resonances of the single tyrosine residue of oxytocin were observed to broaden significantly, but not to shift appreciably, on the addition of neurophysin II. These observations may indicate involvement of the tyrosyl residue of oxytocin in the hormone-"carrier protein" interaction.
 ...
PMID:Drug-biomolecule interactions: proton magnetic resonance studies of complex formation between bovine neurophysins and oxytocin at molecular level. 23 93

The NH exchange rates in aqueous media of oxytocin and 8-lysine vasopressin (LVP) have been measured by using transfer of solvent saturation method. The data are consistent with a "highly motile" dynamic equilibrium between folded and highly solvated conformations. The highly-motility limit applies to the exchange of NH hydrogens of oxytocin and LVP. Folded structures are more prevalent in oxytocin than in LVP. Partial shielding is indicated for peptide hydrogens of Asn5 and perhaps also Cys6 of oxytocin and for Cys6 of LVP. It is tentatively proposed that the folded conformation of oxytocin in aqueous media may contain a parallel beta-structure in the tocinamide ring consisting of two hydrogen bonds: one between the Tyr2 C = O and Asn5 peptide NH as originally proposed for the preferred conformation of oxytocin in dimethyl sulfoxide (D. W. Urry and R. Walter), and the second between he Cys1 C = O and the Cys6 NH. In LVP the hydrogen bond between the Tyr2 C = O and Asn5 peptide NH appears to be absent. The acylic tripeptide sequences (-Pro-X-Gly-NH2) of both hormones appear to be predominantly solvated. The second-order rate constants for acid catalyzed exchange of the primary amide hydrogens of Gln4, Asn5, and Gly9 of oxytocin are consistently greater for the trans NH than for the corresponding cis NH. This observation can be rationalized in terms of mechanisms involving protonation of either the amide oxygen, or the amide nitrogen, but with limited rotation about the C - N bond.
 ...
PMID:Amide hydrogen exchange rates of peptides in H2O solution by 1H nuclear magnetic resonance transfer of solvent saturation method. Conformations of oxytocin and lysine vasopressin in aqueous solution. 26 22

Deamino-[8-N-methylleucine]oxytocin and deamino-[8-alpha-hydroxyisocaproic acid]oxytocin were synthesized to study the importance of hydrogen bonding between the carboxamide carbonyl of asparagine and the peptide N-H of leucine in stabilizing the biologically active conformation of oxytocin. The analogs were synthesized by coupling deaminotocinoic acid with Pro-Leu(Me)-Gly-NH2 and Pro-HyIc-Gly-NH2, respectively. (HyIc is alpha-hydroxyisocaproic acid). Deamino-[8-N-methylleucine]oxytocin was found to possess 48 +/- 7 units of uterotonic activity, 33 +/- 5 units of avian vasodepressor activity, and 3.15 +/- 1.5 units of antidiuretic activity per mg; deamino-[8-alpha-hydroxyisocaproic acid]oxytocin possessed 134 +/- 12 units of uterotonic activity, 31 +/- 3 units of avian vasodepressor activity, 9.6 +/- 3.0 units of antidiuretic activity, and 0.26 +/- 0.02 unit of pressor activity per mg. Neither of the analogs possesses the peptide N-H at residue 8 required for the formation of a hydrogen bond with the asparagine carboxamide; however, both can assume the conformation needed to evoke the characteristic biological activities of oxytocin although in lower potency. It is concluded that such a hydrogen bond does not constitute a conformational constraint that is essential for hormone action.
 ...
PMID:Biofunctional evaluation of a hydrogen bond linking the ring and tail beta-turns of oxytocin. 29 Oct 4

1-Deamino-4-glu-oxytocin (1-beta-mercaptopropionic acid-4-glutamic acid - oxytocin) was synthesized by sequential reduction by sodium in liquid ammonia and oxidation by hydrogen peroxide of the octapeptide derivative, S-benzyl-beta-mercaptopropionyl-tyrosyl-isoleucyl-gamma-O-benzyl-glutamyl-asparaginyl-S-benzyl-cysteinyl-prolyl-leucyl-glycinamide. The oxidation analogue was isolated and purified by partition chromatography in two different solvent systems followed by exclusion chromatography on Sephadex G-25. It was found to possess approximately 13 I.U. of uterotonic activity, 34 I.U. of milk ejection activity, and 83 I.U. of milk ejection-like activity per milligram, measured on an isolated strip of lactating mouse mammary gland. 1-Deamino-4-Glu-oxytocin was coupled to AH-Sepharose 4B by the way of the free gamma-carboxyl group of its residue of glutamic acid. The water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride caused the coupling with approximately 70% effectiveness. The resultant peptide-agarose complex had low biological potency in the assay of milk ejection-like activity.
 ...
PMID:Synthesis and some biological properties of 1-deamino-4-glu-oxytocin (1-beta-mercaptopropionic acid-4-glutamic acid-oxytocin) and its use in preparing a hormone-agarose complex. 112 Feb 87

Proton nuclear magnetic resonance was used to study individual molecules of hydration water bound to the protein basic pancreatic trypsin inhibitor (BPTI) and to the nonapeptide oxytocin in aqueous solution. The experimental observations are nuclear Overhauser effects (NOE) between protons of individual amino acid residues of the protein and those of hydration water. These NOEs were recorded by two-dimensional (2D) and three dimensional (3D) NOE spectroscopy (NOESY) in the laboratory frame, and by the corresponding experiments in the rotating frame (ROESY). The studies show that there are two qualitatively different types of hydration sites. Four water molecules in the interior of the BPTI molecule are in identical locations in the crystal structure and in solution. Their NOEs with the protein protons are characterized by large negative cross-relaxation rates sigma NOE, which indicates that the residence times of the water molecules in these hydration sites are longer than ca. 10 ns. Additional experiments with extrinsic shift reagents established an upper limit of 20 ms at 4 degrees C for these residence times. Surface hydration of both the globular protein BPTI and the flexibly disordered polypeptide oxytocin is by water molecules with residence times in the subnanosecond range, as evidenced by small positive sigma NOE values observed for their NOEs with nearby polypeptide protons. Short residence times prevail for all surface hydration sites, independent of whether or not they are occupied by well ordered, X-ray observable water in the protein single crystals.
 ...
PMID:Protein hydration in aqueous solution. 128 62

The effect of excitatory amino acid receptor antagonists, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate ((+)-MK-801), (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (+/-)-2-amino-4-phosphonobutanoic acid (AP-4), on penile erection and yawning induced by subcutaneous apomorphine (80 micrograms/kg), intracerebroventricular (i.c.v.) oxytocin (30 ng) and adrenocorticotropin (ACTH)-(1-24) (10 micrograms) was studied in male rats. Intraperitoneal (0.1-0.4 mg/kg) and i.c.v. (10-50 micrograms) (+)-MK-801 prevented dose dependently the penile erection and yawning induced by the three drugs. The (+)-MK-801 effect coincided with the appearance of head weaving, body rolling, hyperlocomotion and ataxia. Haloperidol (0.5 mg/kg i.p.) antagonized the prevention by (+)-MK-801 of oxytocin responses. Penile erection but not yawning was also prevented by high, but not low doses of CPP and CNQX, which impaired motor performance, AP-4 was ineffective at all doses tested. The above compounds were ineffective when injected into the paraventricular nucleus of the hypothalamus, the brain area where apomorphine and oxytocin act to induce penile erection and yawning. The results suggest that excitatory amino acid transmission is not involved in the expression of penile erection and yawning induced by the above compounds.
 ...
PMID:Effect of excitatory amino acid receptor antagonists on apomorphine-, oxytocin- and ACTH-induced penile erection and yawning in male rats. 135 47

The conformation of oxytocin, the neurohypophyseal nonapeptide hormone, in solution in deuterated dimethyl sulfoxide has been determined by 1H-nmr. The structural determination is based on the experimental data set of nuclear Overhauser effect restraints. Obtained after the restrained molecular dynamics simulation on an initial structure of extended conformation, five resultant structures satisfy the experimental restraints well. These structures resemble that of the crystal structure of deamino-oxytocin, an analogue of oxytocin, in terms of a close correlation observed both at two beta-turn regions of the 20-membered tocin ring and at the tripeptide tail end. Based on this comparison and analysis of restrained molecular dynamics trajectories, we found that, although the turns are stabilized by the formation of hydrogen bonds, the oxytocin molecule possesses a slight twist in DMSO solution relative to the orientation of deamino-oxytocin in the crystalline state. Analyses of oxytocin conformation indicate that the tripeptide tail is more flexible than the tocin ring.
 ...
PMID:Conformational properties of oxytocin in dimethyl sulfoxide solution: NMR and restrained molecular dynamics studies. 147 46


1 2 3 4 5 6 7 Next >>