UNIPROT:P01178 - FACTA Search

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

Neuropeptides and biogenic amines known to be present in neurons or afferent terminals in the paraventricular nucleus (PVH), supraoptic nucleus (SON) and/or lateral hypothalamus (LH) were added to small areas of these structures obtained by micropuncture and cyclic adenosine monophosphate (cAMP) levels were measured. cAMP accumulation occurred in PVH, SON and LH in response to neuropeptides of the secretin family, such as vasoactive intestinal peptide (VIP) and in response to catecholamines. Bradykinin, alpha-melanocyte-stimulating (alpha-MSH), luteinizing hormone-releasing hormone (LH-RH), oxytocin and carbamylcholine stimulated cAMP accumulation selectively in one or two of the above structures. Glucagon, cholecystokinin (CCK), somatostatin (SRIF), corticotropin-releasing factor (CRF), thyrotropin-releasing hormone (TRH), adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH), methionine enkephalin (Met-Enk), beta-endorphin, neurotensin, bombesin and angiotensin II did not effect cAMP levels while leucine enkephalin (Leu-Enk), arginine vasopressin and gamma-aminobutyric acid (GABA) elicited regionally selective decreases in basal levels of cAMP. When interactions between some of these compounds were measured, VIP and norepinephrine exerted a more than additive effect on cAMP elevation in the PVH, while the effect on cAMP of the SON and LH was additive.
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PMID:Interaction of neuropeptides and biogenic amines on cyclic adenosine monophosphate accumulation in hypothalamic nuclei. 300 57

The distribution of FMRFamidelike peptides was studied in the nervous system of the lobster Homarus americanus by using immunocytochemical and radioimmunological techniques. By radioimmunoassay FMRFamidelike immunoreactivity (FLI) was found in low levels (ca. 1 pmol/mg protein) throughout the ventral nerve cord and in much higher amounts (60-100 pmol/mg protein) in the neurosecretory pericardial organs. Immunocytochemical studies showed FLI in approximately 300-350 cell bodies, and in distinct neuropil regions, neuronal fiber tracts, and varicose endings. Specificity of the immunostaining was tested by preabsorbing the antiserum with FMRFamide, with peptides having similar carboxyl termini to FMRFamide (Met-enkephalin-Arg-Phe, Phe-Met-Arg-Tyr-amide), with several amidated peptides (alpha-melanocyte-stimulating hormone, substance P, oxytocin), and with proctolin, a peptide found widely distributed in the lobster nervous system. Of these substances, only FMRFamide blocked the staining. In addition to the pericardial organs, significant levels of FLI were found in neurosecretory regions associated with thoracic second roots and in the connective tissue sheath that surrounds the ventral nerve cord. In all three regions, immunocytochemical studies showed the FLI to be localized to fine fibers and associated terminal varicosities lying close to the surface of the tissue, with no obvious target in their immediate vicinity. When examined at the ultrastructural level, the immunoreactive varicosities of the thoracic second roots and of the ventral nerve cord sheaths were found a few microns from the surface of the tissue and contained electron-dense granules. In the immunoreactive nerve cord sheath endings, in addition to the large, dense granules, small, clear vesicles were found. The appearance and location of these terminals suggest a neurohormonal role for FMRFamidelike peptides in lobsters. The observation that low levels of FLI are found in the hemolymph supports this suggestion. In addition, the localization of FLI to particular neuronal somata, fiber tracts, and neuropil regions suggests possible functional roles for these peptides in (1) integration of visual and olfactory information, (2) function of the anterior and posterior gut, and (3) the control of exoskeletal muscles.
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PMID:FMRFamidelike peptides of Homarus americanus: distribution, immunocytochemical mapping, and ultrastructural localization in terminal varicosities. 332 67

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 effect of 15 defined neuropeptides on the mitogenic activation of lymphocytes from human thymus, guinea pig lymph nodes and rat spleen was investigated. Lymphocytes were incubated in the absence or presence of polyclonal T and B cell activators together with increasing doses of the neuropeptides, and harvested at 48 h of culture after pulse-labeling with 3H-thymidine to assess the DNA synthesis. A dose-related stimulatory effect on the spontaneous 3H-thymidine incorporation of human thymocytes was obtained with methionine-enkephalin (met-enk), motilin and neurotensin. Vasoactive intestinal polypeptide (VIP) and peptide HI (PHI) were inhibitory. A similar responsiveness was observed in cultures of phytohemagglutinin P (PHA)-activated human thymocytes. The low level of basal DNA synthesis of guinea pig lymph node cells was stimulated by VIP and inhibited by neuropeptide Y (NPY) and PHI. PHA-activated lymph node T lymphocytes were stimulated by neurotensin, bombesin and motilin, whereas NPY inhibited the thymidine uptake. The low rate of spontaneous DNA synthesis of rat spleen cells was increased in the presence of VIP. Met-enk stimulated both basal and dextran sulfate-activated splenic B cell proliferation, whereas PHI was inhibitory in both cases. The following peptides were found to be inactive in all the above assays: substance P, cholecystokinin-octapeptide, somatostatin, galanin, oxytocin, pentagastrin and gastrin-releasing peptide 1-27 and 14-27. Although the responses were generally of low magnitude and observed at high peptide concentrations, present study contributes to the understanding of possible mechanisms involved in interactions between the nervous and the immune system.
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PMID:Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. 349 94

Photoaffinity labeling of the single neurophysin tyrosine, Tyr-49, with Met-Tyr-azido-Phe amide has been reported to inhibit both neurophysin self-association and peptide binding. Accordingly, we investigated the functional consequences of modification, principally by tetranitromethane, of Tyr-49. Tetranitromethane-mediated tyrosine-tyrosine cross-linking permitted synthesis of covalent neurophysin "dimers" and of peptide-protein conjugates, the latter potentially analogous to the photoaffinity-labeled product. The self-association and binding properties of the covalent dimers were found to be similar or enhanced relative to those of the native protein. In contrast to the photoaffinity-labeled product, covalent conjugates of Tyr-49 with the ligand peptides Met-Phe-Tyr amide, Phe-Tyr amide, and Tyr-Phe amide also generally exhibited normal or increased binding affinity for exogenous peptide; a subfraction of the Phe-Tyr amide adducts showed evidence of reduced affinity. Diiodination of Tyr-49 had no significant effect on binding. However, among the products of tetranitromethane treatment in the absence of peptide was a novel inactive non-cross-linked product, representing modification only of Tyr-49 but containing no demonstrable nitrophenol. As evidenced by circular dichroism and nuclear magnetic resonance (NMR), this product was not significantly unfolded and retained the ability to self-associate. These latter results provide the strongest evidence thus far of a role for Tyr-49 in peptide-hormone binding. The disparate effects of different Tyr-49 modifications are collectively interpreted and reconciled with NMR data and the properties of the photoaffinity-labeled protein to suggest potential mechanisms of Tyr-49 participation in binding and the probable orientation of Tyr-49 relative to peptide residue 3 in neurophysin complexes.
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PMID:Chemical modification and cross-linking of neurophysin tyrosine-49. 356 65

The structural organization of neurohypophysial hormone biosynthetic precursors and the interdependence between intramolecular folding and precursor self-association were examined using sequence-engineered mutants of the semisynthetic oxytocin/bovine neurophysin precursor (pros-OT/BNPI). In [N alpha 1-Ac,N epsilon 30,71-diacetimidyl, Ala2,des-His106] Pro-Ot/BNPI or [N alpha 1-Ac,Ala2]pros-OT/BNPI), two structural elements (Tyr2 and free alpha-amino group) were eliminated which were predicted to be critical for intramolecular conformation by stabilizing contact between hormone and neurophysin domains. This mutant was used to test the dependence of precursor self-association on intramolecular conformation. In the second mutant precursor, [N alpha 30,71-diacetimidyl,D-Pro7,D-Leu8,des-His106]p ro-OT/BNPI (or [D-Pro7,D-Leu8]pros-OT/BNPI), the stereochemistry at L-Pro7-L-Leu8 was changed to test the extent to which precursor conformation depends on ordered structure in the processing/spacer sequence which connects the interacting hormone and neurophysin I domains. Intramolecular conformation was characterized for the precursor and mutants by analytical affinity chromatography on immobilized hormone analog Met-Tyr-Phe and by circular dichroism. Data obtained by both methods showed that, while pros-OT/BNPI is folded, with hormone domain occupying the hormone-binding site of the neurophysin domain, the alpha-acetyl-Ala2 mutant is not so organized intramolecularly. When pros-OT/BNPI and the alpha-acetyl-Ala2 mutant were eluted on immobilized BNPII to measure self-association propensity, the native-like precursor was found to bind with 12-15-fold higher affinity than the assembly mutant. Thus, while pros-OT/BNPI assumes a molecular structure containing a high-affinity self-association surface induced by intramolecular hormone domain-neurophysin domain interaction, [N alpha 1-Ac,Ala2]pros-OT/BNPI does not. The results with the alpha-acetyl-Ala2 mutant show that intramolecular domain-domain interaction is the obligatory "trigger" which induces the high-affinity precursor self-association that likely drives precursor to aggregated forms in the concentrated intragranular environment that exists in peptide hormone-synthesizing cells. In contrast, affinity chromatographic and circular dichroism properties of the D-Pro7,D-Leu8 mutant show that this intramolecular trigger is dependent, but only weakly, on the conformation of the peptide sequence between domains, as judged by native-like interaction properties below 40 degrees C but lowered stability to elevated temperature.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sequence redesign and the assembly mechanism of the oxytocin/bovine neurophysin I biosynthetic precursor. 365 97

In vitro stimulation of intact rat posterior pituitary by either veratridine or K+ depolarization results in the concomitant release of neurophysins and in a decrease (70-80%) in their carboxyl methylation as measured either with L-[methyl-3H]methionine in the intact lobes after stimulation or in their homogenates with [methyl-3H]S-adenosyl-L-methionine and purified protein carboxyl methyltransferase. A similar reduction in neurophysin methylation (60%) was observed when the arrival of newly synthesized neurophysins at the posterior pituitary was blocked by colchicine. Experimental data indicate that the reduction in neurophysin content of the lobes after 12 h of colchicine treatment (less than 7%) or after in vitro stimulation (about 10%) cannot account for the marked reduction in neurophysin methylation. The results suggest that the granule pool characterized by rapid turnover of neurophysins probably represents the major source of methyl acceptor proteins in the lobe. In spite of the marked reduction in neurophysin methyl accepting capacity observed after stimulation, there was no parallel increase in methyl accepting capacity of the released neurophysins. We propose that a neurophysin subfraction that might be associated with the membrane of releasable granules participates in the methylation reaction in situ.
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PMID:Enzymatic protein carboxyl methylation in rat posterior pituitary: neurophysins in rapid-turnover pool determine methyl accepting capacity. 379 1

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

An oxytocin/bovine neurophysin I biosynthetic precursor, [N epsilon-diacetimidyl-30,71, des-His106]pro-OT/BNPI, was synthesized from a synthetic oxytocinyl peptide, 1/2Cys-Tyr-Ile-Gln-Asn-1/2Cys-Pro-Leu-Gly-Gly-Lys-Arg, and native neurophysin by chemical semisynthesis. The semisynthetic precursor contains the entire sequence of the biosynthetic precursor deduced from the complementary DNA structure except for omission of the carboxyl-terminal histidine residue. The covalent structure of the semisynthetic product was verified by amino acid analysis and amino-terminal analysis. Analytical affinity chromatography was employed to evaluate noncovalent binding properties of the precursor. The precursor does not bind significantly to immobilized Met-Tyr-Phe, a hormone binding site ligand. In contrast, the acetimidated precursor binds to immobilized bovine neurophysin II, with a 13-fold higher affinity than does acetimidated neurophysin itself. When a hormonal ligand, [Lys8]vasopressin, was added to the elution buffer at the concentration of 0.1 mM so that a major portion of the immobilized BNPII was liganded, the affinity between the immobilized liganded BNPII and the precursor was enhanced 8-fold and approached the affinity for the liganded (bovine neurophysin I-immobilized BNPII) interaction. The data imply that the precursor can self-associate and that this self-association is closely related to that of liganded neurophysin. The tripeptide affinity matrix data argue that, in the precursor, the ligand binding site of the neurophysin domain is occupied intramolecularly by the hormone domain. The data verify the view that both the self-association surface and hormone binding site are established upon precursor folding. A disulfide stability analysis showed the resistance, to disulfide interchange by dithiothreitol, of semisynthetic precursor but not of neurophysin, as judged by protein association and peptide ligand binding activities, respectively. The results argue that the molecular structure of the precursor is established upon precursor folding and before enzymatic processing that produces mature hormone and neurophysin.
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PMID:Molecular properties of the oxytocin/bovine neurophysin biosynthetic precursor. Studies using a semisynthetic precursor. 400 99

To determine differential tissue antigens in the same section immunocytochemically using the electron microscope, the neurohypophysis was examined following the application of a freeze-drying tissue preparation and staining with the protein A-colloidal gold-antibody complex method (Hisano S, Adachi T, Daikoku S: J Histochem Cytochem 32:705, 1984). At the light microscopic level, colocalized immunostaining for methionine-enkephalin (ENK) and oxytocin (OXT) was found in the rat neurohypophysis under different physiological states. Small pieces of the neurohypophysial tissue were frozen and dried. The dried tissue was fixed with paraformaldehyde vapor and embedded. The ultrathin sections were stained with the antibody for ENK coupled with protein A-small colloidal gold, and antibody for OXT or vasopressin (VP) conjugated with protein A-large colloidal gold. The ultrastructures of the nerve terminals were well preserved and showed many membrane-limited secretory granules. It was possible to identify both OXT- and VP-containing nerve terminals as their secretory granules were differentially labeled with protein A-colloidal gold anti-OXT or anti-VP complex, respectively. The secretory granules, which were labeled with large gold particles for OXT, also carry small gold particles. It is evident that ENK coexists with OXT in the same granules.
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PMID:Intragranular colocalization of immunoreactive methionine-enkephalin and oxytocin within the nerve terminals in the posterior pituitary. 402 Jan

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