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 effect of ovine trophoblast protein-one (oTP-1) on endometrial protein secretion was examined by using a dual radioisotope technique in which 3H- and 35S-methionine were employed to measure relative rates of protein release into the medium by endometrial explant cultures (Exp. I). Endometrium (200 mg) from Day (D) 12 of the cycle was cultured with either 5 micrograms/ml oTP-1, 5 micrograms/ml bovine serum albumin (BSA) or 1 mM dibutyryl cyclic adenosine 3',5'-monophosphate (DbcAMP). Culture media from control BSA and treated explant cultures were mixed. Proteins were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and detected by fluorography. Individual protein spots were punched from gels, extracted, and their radioactive content measured. Ratios of 3H:35S were used to determine treatment effects. In Experiment II, 3H- and 14C-leucine were used for the dual radiolabel, and the DbcAMP treatment was omitted. In both experiments, a protein having a molecular weight (Mr) of about 70,000 and a pI approximately equal to 4 was increased (p less than 0.01) 200-400% by oTP-1. Secretion of several other endometrial proteins was also amplified in the presence of oTP-1. The polypeptides that increased in response to oTP-1 were inhibited by DbcAMP, and vica versa. In Experiment III, endometrial explants from D12 cyclic ewes were cultured for 4 h with either 5 micrograms/ml oTP-1 or 5 micrograms/ml BSA to determine whether oTP-1 influenced concentrations of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). Concentrations of cAMP in oTP-1-treated endometrium were lower (p less than 0.1) than in BSA-treated endometrium (0.29 vs. 0.41 pmoles/mg tissue, respectively). Levels of cGMP were unaffected by oTP-1. In Experiment IV, endometrium from D14 of the cycle was incubated in medium alone or in medium containing either 2 micrograms/ml oTP-1, 1 microgram/ml oxytocin (OXY), or oTP-1-plus-OXY. None of the treatments significantly affected cAMP levels. In Experiment V, D16 endometrium was collected from pregnant and nonpregnant ewes that had received either 0 or 10 IU OXY i.v. cAMP was higher (p less than 0.01) in endometrium from pregnant ewes compared to nonpregnant ewes (27.9 vs. 13.0 pmoles/mg tissue, respectively), but OXY had no detectable effect on endometrial content of cAMP in either nonpregnant or pregnant ewes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of ovine trophoblast protein-one on endometrial protein secretion and cyclic nucleotides. 344 99

The octacosapeptide sequence [Tyr18] pro-ocytocin/neurophysin (1-18)NH2 [pro-OT/Np(1-18)NH2] was synthesized and used as substrate to detect endoprotease(s) possibly involved in the processing of this precursor in bovine hypothalamo-neurohypophyseal tract. An endopeptidase (58 Kda) was detected in Lysates made from highly purified neurosecretory granules. This protease which cleaves the peptide bond on the carboxyl side of the Lys-Arg doublet, and no single basic residue, generates both OT-Gly10-Lys11-Arg12+Ala13-Val-Leu-Asp-Leu-Tyr18 (NH2) from the octacosapeptide substrate. In addition, a carboxypeptidase B-like activity converting OT-Gly10-Lys11-Arg12 into OT-Gly10 was detected in the same granule Lysates. It is hypothesized that a combination of these endoprotease and carboxypeptidase B-like activities together with the amidating enzyme of secretory granules might participate in the cleavage and processing of pro-OT/Np in vivo.
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PMID:An endopeptidase associated with bovine neurohypophysis secretory granules cleaves pro-ocytocin/neurophysin peptide at paired basic residues. 351 14

Rat neurointermediate lobes and neurohypophyses separated from the pars intermedia were stimulated in vitro in the presence of either D-Ala2, D-Leu5-enkephalin (DADLE), a Leu-enkephalin stable analogue or FK 33-824 a Met-enkephalin stable analogue. Secretion of vasopressin (AVP) and oxytocin (OT) was produced by either a Ca2+-ionophore or with electrical stimulation or by K+-induced depolarization. These opioid peptides and their antagonist naloxone did not affect basal nor evoked hormone release. Furthermore, they did not affect the evoked calcium uptake induced with electrical stimulation. These findings were confirmed using a preparation of isolated neurosecretory nerve endings. Further, dopamine had no effect on the K+-induced AVP release although a crude extract of the pars intermedia abolished the electrically-evoked and reduced considerably the potassium-evoked AVP release. It is concluded that in the neurohypophysis neither Leu- and Met-enkephalin nor dopamine affect the secretion-coupling mechanism at the level of the neurosecretory nerve endings.
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PMID:Do opioid peptides modulate, at the level of the nerve endings, the release of neurohypophysial hormones? 351 53

Perdeuteriated peptides were synthesized that are capable of binding to the hormone binding site of neurophysin but that differ in the position of aromatic residues. The binding of these peptides to bovine neurophysin I and its des-1-8 derivative was studied by proton nuclear magnetic resonance spectroscopy in order to identify protein residues near the binding site through the observation of differential ring current effects on assignable protein resonances. Phenylalanine in position 3 of bound peptides was shown to induce significant ring current shifts in several resonances assignable to the 1-8 sequence, including those of Leu-3 and/or Leu-5, but was without effect on Tyr-49 ring protons. The magnitude of these shifts was dependent on the identity of peptide residue 1. By contrast, the sole demonstrable direct effect of an aromatic residue in position 1 was a downfield shift in Tyr-49 ring protons. Study of peptide binding to des-1-8-neurophysin demonstrated similar conformations of native and des-1-8 complexes except for the environment of Tyr-49, confirmed the peptide-induced ring current shift assignments in native neurophysin, and indicated an effect of binding on Thr-9. These observations are integrated with other results to provide a partial model of neurophysin-peptide complexes that places the ring of Tyr-49 at a distance 5-10 A from residue 1 of bound peptide and that places both the 1-8 sequence and the protein backbone region containing Tyr-49 proximal to each other and to peptide residue 3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Application of peptide-mediated ring current shifts to the study of neurophysin-peptide interactions: a partial model of the neurophysin-peptide complex. 359 76

A brain to blood carrier-mediated transport system for arginine vasopressin (AVP) was investigated in mice after intraventricular injection of iodinated AVP and varying amounts of unlabeled material or candidate inhibitors. Residual activity in the brain detected after decapitation was used as the main determinant of transport activity. The half-time disappearance of iodinated AVP from the brain was 12.4 min, the Vmax was 1.41 nmol/g-min, and the apparent Km was 28.7 nmol/g. A 30-nmol dose of AVP, mesotocin, arginine vasotocin, pressinoic amide, pressinoic acid, tocinoic acid, and lysine vasotocin, but not oxytocin, lysine vasopressin, AVP free acid, tocinoic amide, Tyr-MIF-1, or cyclo Leu-Gly, significantly (P less than 0.05) inhibited the transport of iodinated AVP out of the brain. The 30 nmol dose of AVP had no effect on the transport of iodide or iodotyrosine out of the brain. High-performance liquid chromatography showed that 59.2% of the radioactivity found in the blood 2 min after an i.c.v. injection of labeled AVP eluted at the same position as labeled AVP compared with 68.8% of radioactivity eluting at that position after material was infused i.v. for 2 min. This indicates that intact peptide is transported across the blood-brain barrier and that most of the degradation of AVP occurs during circulation in the blood. Calculations based on the appearance of radioactivity in the periphery showed that 56.2% of the material injected centrally would have been transported into the periphery by 10 min. This appearance of material in the periphery was inhibited by the simultaneous injection of an excess of unlabeled peptide. Water loading significantly decreased the brain to blood transport rate of AVP by 40%. It is concluded that a saturable system exists for brain to blood transport of AVP and some structurally similar peptides.
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PMID:Carrier-mediated transport of vasopressin across the blood-brain barrier of the mouse. 369 15

The axonal efferents of neurons of the supraoptic nucleus area were studied by radioautography in the rat after discrete stereotaxic injections of [3H]leucine into this nucleus. Beside a densely labeled pathway running from the nucleus to the posterior pituitary through the internal median eminence, several of the visualized labeled axonal bundles were found to project into various extrahypothalamic regions, including the olfactory bulb, the cortex, the lateral habenula, the subcommissural organ, the amygdala, the mammillary bodies and the locus coeruleus. These results suggest that part of the vasopressin- or oxytocin-containing perikarya located in the supraoptic nucleus constitute the cells of origin of axons which also contain these peptides and which have already been shown to be present in the above extrahypothalamic areas. This also implies that, like the paraventricular nucleus, the supraoptic nucleus is also involved in central extrahypothalamic regulations.
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PMID:Radioautographic evidence that axons from the area of supraoptic nuclei in the rat project to extrahypothalamic brain regions. 372 90

A chemical method has been established for the detection of carboxyl-terminally amidated peptides in tissue extracts. Tissue was homogenized in an acidic medium designed to solubilize peptides while precipitating high-molecular-weight protein. The homogenate supernatant was in turn subjected to reversed-phase extraction with C18 Sep-Pak cartridges. The eluates were fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC). Individual fractions were exhaustively digested with thermolysin, derivatized with phenylisothiocyanate (PITC), and then subjected to ethyl acetate extraction under basic conditions. The phenylthiocarbamyl (PTC)-amino acid amide derivatives were selectively taken up into the organic phase, while the other digestion products remained in the aqueous phase. The organic phase was analyzed by RP-HPLC on a Pico-Tag amino acid analysis column, monitoring eluates at 254 nm. PTC-amino acid amides were identified and quantitated by comparing their elution positions and peak areas, respectively, with those of standards. Their identities were confirmed by amino acid analysis, following hydrolysis with hydriodic acid. The technique was applied to extracts of bovine posterior pituitaries and a human medullary thyroid carcinoma. Vasopressin (-Leu-Gly-amide), oxytocin (-Gly-amide), Lys1 gamma 1-melanotropin (-Phe-amide), and various acetylated and non-acetylated forms of alpha-melanotropin (-Val-amide) were identified in the posterior pituitary extract. Various forms of calcitonin (-Val-Gly-Ala-Pro-amide) were detected in the tumour extract. For vasopressin and calcitonin the thermolytic digest resulted in di- and tetra-peptides, respectively, reflecting thermolytic cleavage at more favoured sites.
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PMID:Use of Pico-Tag methodology in the chemical analysis of peptides with carboxyl-terminal amides. 373 29

The effects of graded doses of a substituted tripeptide analogue of the C-terminal part of oxytocin, D-Pip-Leu-GlyNH2 (DPLG), were investigated on the development of tolerance to the hypothermic effect of and dependence on alcohol in mice. Ethanol injection (4 g/kg i.p.) repeated on 3 consecutive days led to the development of tolerance in control and peptide-treated (0.005 microgram/mouse) animals. In the latter group, however, the level of tolerance was lower than in the control animals. The higher doses (0.05-5.0 micrograms/mouse) inhibited the development of tolerance. Repeated peptide administrations (5, 25, 125 micrograms/animal) did not affect the development of the dependence on alcohol which resulted from combined daily injections of tert-butanol (1.5 g/kg i.p.) and ethanol (3 g/kg i.p.). The severity of withdrawal was quantified via the convulsions induced with different doses of picrotoxin. When the peptide was injected only before the testing of withdrawal, DPLG markedly prolonged the onset of withdrawal signs.
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PMID:D-pipecolyl-leucyl-glycinamide, a substituted tripeptide analogue of the C-terminal part of oxytocin, influences tolerance to and dependence on ethanol in mice. 377 81

From guinea pig posterior pituitaries, a MSEL-type neurophysin (neurophysin containing methionine-2, serine-3, glutamic acid-6 and leucine-7), a glycopeptide referred to as copeptin and their common precursor have been purified to homogeneity and sequenced. The performed acid-oxidized precursor, subjected to trypsin hydrolysis, has given 9 peptides, 6 of which (T1-T6) identical to those given by oxidized MSEL-neurophysin except that T6 has an additional C-terminal arginine residue when compared to its homologue. The other 3 tryptic peptides (T7-T9) are identical to those given by copeptin. The 132-residue precursor therefore comprises a MSEL-type neurophysin (93 residues) and copeptin (38 residues) linked by an arginine residue. The molar proportion of this bound form compared with the free polypeptides is approximately 20%. It is believed that this precursor is a part of the vasopressin-MSEL-neurophysin-copeptin precursor incompletely processed during the transport from hypothalamus to neurohypophysis.
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PMID:Structure of a guinea pig common precursor to a MSEL-type neurophysin and copeptin. 395 54

The effects on bovine neurophysin-I of binding the perdeuterated peptides Phe-PheNH2 and Leu-PheNH2 were compared by proton NMR. A unique difference between the two peptides in their effects on Tyr-49 ring protons indicated proximity of the Tyr-49 ring to the side-chain of position 1 of bound peptide. Non-deuterated oligopeptides containing Phe in position 3 and no methyl groups induced different changes in neurophysin methyl resonances than dipeptides, suggesting shielding of one or more protein methyl groups by Phe-3. The results demonstrate that the identity of neurophysin residues at the hormone-binding site can be probed by analysis of changes induced in the protein spectrum by systematically related NMR-transparent peptides.
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PMID:Use of perdeuterated peptides in NMR studies of neurophysin-hormone interaction: demonstration of peptide-specific changes in neurophysin resonances. 400 58


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