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 guinea pig two-domain precursor of MSEL-neurophysin and copeptin has been passed through a trypsin-Sepharose column in order to mimic the enzyme processing by a membrane-bound endopeptidase. Only two cleavages were observed located in the inter-domain sequence (at Arg-94 and Arg-98), in contrast to several additional cleavages found when free neurophysin or copeptin is subjected to soluble trypsin. Because the physiological maturation involves a single cleavage at Arg-94, both local accessibility in the precursor and narrow specificity of the enzyme are implied in the processing.
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PMID:Conformation limited proteolysis in the common neurophysin-copeptin precursor shown by trypsin-sepharose chromatographic proteolysis. 359 48

The axonal endoplasmic reticulum (ER) and synaptic-like (micro)vesicles within axon terminals of the neurohypophysis and their contribution to the secretory process in hypothalamo-neurohypophysial neurons have been investigated cytochemically in normal mice and in mice given 2% salt water to drink for stimulation of hormone synthesis in and release from these neurons. Cytochemical techniques included the peroxidase-antiperoxidase (PAP) immunocytochemical method for localization of neurophysin, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a tracer for the anterograde axonal transport of membrane from within the perikaryon, and blood-borne native horseradish peroxidase (HRP) as a tracer for internalized axon terminal membrane. The primary antiserum employed was directed against neurophysins I and II, the carrier proteins for the peptide hormones oxytocin and vasopressin, respectively. PAP reaction product was observed over neurosecretory granules but never over the endoplasmic reticulum, microvesicles or other organelles in axons and terminals of the neurohypophysis. WGA-HRP was delivered extracellularly to cell bodies of paraventricular neurons by cerebral ventriculocisternal perfusion. Internalized perikaryal surface membrane tagged with WGA-HRP was recycled through the innermost Golgi saccule (GERL) from which neurosecretory granules were formed. The anterograde axonal transport of membrane-bound WGA-HRP was manifested within the neurosecretory granules; WGA-HRP did not label the axonal reticulum or terminal microvesicles in the neurohypophysis. Blood-borne native HRP endocytosed into neurohypophysial terminals was associated with a plethora of microvesicles measuring 40-70 nm in diameter and vacuoles similar in size to the 100-300-nm-wide neurosecretory granules. The microvesicles contributed to the formation of numerous vacuoles. The internalization of axon terminal membrane as microvesicles incorporating HRP was quantitatively greater than vacuoles in both salt-stressed and control mice. The results suggest that in the hypothalamo-neurohypophysial system of the mouse the axonal ER and terminal microvesicles are not involved in the transport, storage, and exocytosis of neurosecretory material and perhaps other molecules processed through the innermost Golgi saccule. Nevertheless, a prominent population of the microvesicles within axon terminals of the neurohypophysis does participate in the secretory process. These vesicles are involved directly in the internalization of the terminal surface membrane subsequent to release of secretory granule content.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Further studies of the secretory process in hypothalamo-neurohypophysial neurons: an analysis using immunocytochemistry, wheat germ agglutinin-peroxidase, and native peroxidase. 620 13

mRNA from membrane-bound polysomes of bovine hypothalamus was translated in an mRNA-dependent cell-free system from reticulocyte lysate or wheat germ. The translation products were identified by immunoprecipitation with antibodies to either neurophysin II or arginine vasopressin followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. An immunoreactive polypeptide was obtained with an apparent Mr of 21,000. Sequential immunoprecipitation studies indicated that the Mr 21,000 product is a common precursor to neurophysin II and arginine vasopressin. The specificity of the immunoprecipitation was demonstrated by competition with excess amounts of unlabeled neurophysin II or arginine vasopressin; little or no competition was observed with unlabeled neurophysin II or arginine vasopressin; little or no competition was observed with unlabeled neurophysin I or oxytocin. Processing experiments with microsomal membranes from dog pancreas or tunicamycin-treated ascites tumor cells showed that the Mr 21,000 polypeptide is the prepro form. It was converted to a pro form with Mr 19,000 suggesting a pre sequence of approximately 15 amino acids. The Mr 19,000 polypeptide was coreglycosylated to an apparent Mr of 23,000, indicating that the neurophysin II-arginine vasopressin precursor is a glycopolypeptide.
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PMID:Immunological identification of a common precursor to arginine vasopressin and neurophysin II synthesized by in vitro translation of bovine hypothalamic mRNA. 694 Jan 45

Previous work demonstrated that human fat-cells possess a plasma-membrane-bound H2O2-generating system that is activated by insulin. Here we show that this system is under antagonistic control by various hormones and cytokines that typically act through several distinct receptor families. Similarly to insulin, oxytocin and tumour necrosis factor alpha acted as stimulators of NADPH-dependent H2O2 generation, whereas isoprenaline, a beta-adrenergic agonist, had inhibitory effects. Surprisingly, the acidic and basic isoforms of fibroblast growth factor as well as homodimeric platelet-derived growth factor AA and BB had antagonistic stimulatory and inhibitory effects on NADPH-dependent H2O2 generation. The agents tested acted at discrete ligand-specific receptors and their mechanisms of action were membrane-delimited and occurred in the absence of ATP. These findings implied that established pathways of signal transduction, including receptor kinases or second-messenger-dependent protein kinases A and C, were not involved and placed the stimulus-sensitive H2O2-generating system in a position comparable with adenylate cyclase. It was concluded that the stimulus-sensitive H2O2-generating system of human fat-cells meets all criteria of a universal signal-transducing system for hormones and cytokines that may link ligand binding to cell-surface receptors to changes in the intracellular redox equilibrium.
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PMID:The stimulus-sensitive H2O2-generating system present in human fat-cell plasma membranes is multireceptor-linked and under antagonistic control by hormones and cytokines. 773 95

The cellular localization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor, GluR3, was identified using antibodies that recognize the N-terminus of the predicted polypeptide sequence of GluR3. Regional immunoblot analysis of monkey brain homogenates identified a protein of approximately 102,000 mol. wt that was enriched in hypothalamus. Immunocytochemistry demonstrated that GluR3 was enriched within the hypothalamic magnocellular neurosecretory nuclei and axons of the hypothalamo-neurohypophysial tract in rat and monkey. GluR3 immunoreactivity co-localized to oxytocin-containing, but not vasopressin-containing, neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus and accessory magnocellular nuclei. Ultrastructurally, GluR3 immunoreactivity was enriched throughout cytoplasm of the somatodendritic compartment and was associated with postsynaptic and presynaptic structures. GluR3 immunoreactivity was frequently observed to be clustered at the plasma membrane of the somatodendritic compartment, consistent with the predicted localization of a membrane-bound ion channel. Additionally, GluR3-immunoreactive axon terminals in synaptic contact with unlabeled dendrites within the retrochiasmatic area and bed nucleus of the stria terminalis were observed, providing morphological evidence for a presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor. By immunoblot analysis and immunocytochemistry using antibodies directed against a specific alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor in rat and monkey brain, our findings suggest a highly selective hypothalamic distribution of the GluR3 subunit that may have functional significance in the glutamatergic regulation of oxytocinergic neurons.
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PMID:The AMPA glutamate receptor GluR3 is enriched in oxytocinergic magnocellular neurons and is localized at synapses. 777 69

Oxytocin proteolysis was studied in vitro with purified synaptic membranes and in vivo after injection into the hippocampus of male Wistar Kyoto rats of different ages. When oxytocin was incubated in vitro with brain synaptic membranes obtained from 2-, 6-, and 12-month-old rats, no difference in the content of C-terminal and N-terminal fragments formed by membrane-bound aminopeptidase-like and endopeptidase-like enzymes, respectively, was found after high performance liquid chromatography separation and quantification by amino acid analysis. In contrast, the content of all fragments decreased by about 20%-25% when membranes obtained from 18- and 24-month-old rats were used. When [3H-Tyr2]oxytocin was injected in vivo in the hippocampus of 2-, 6-, 12-, and 18-month-old rats, no difference in the content of free [3H]-tyrosine and other [3H]-labelled fragments was found in the hippocampal peptidic extract after high performance liquid chromatography fractionation. However, the content of all radioactive fragments was about 50% lower in the extract from 24-month-old rats. The findings suggest that oxytocin proteolysis in brain decreases during aging. Such a decrease might counterbalance the impairment of central oxytocinergic transmission caused by the age-related decrease of oxytocin content in brain.
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PMID:Brain proteolysis of oxytocin in vitro and in vivo changes during aging in male rats. 783 89

Since previous studies in vivo have shown that oxytocin is metabolized by rat synaptic membrane-bound aminopeptidase- and endopeptidase-like enzymes, the proteolytic conversion of oxytocin was studied in vivo after microinjection in the rat hippocampus, a brain area that contains oxytocinergic nerve endings and receptors. Isolation of the formed peptide fragments from the injected brain area after homogenization and adsorption on a Sep-Pak cartridge by high performance liquid chromatography, and their characterization by amino acid analysis, revealed that, when oxytocin (50 nmol in 0.5 microliter) was microinjected in the CA1 field of the rat hippocampus, only the N-terminal fragment oxytocin(1-8) was formed in such amount that could be characterized. The microinjection of [3H-Tyr2]oxytocin (10 pmol) revealed that in addition to oxytocin(1-8), free [3H]tyrosine was formed. Taken together with previous findings showing that C-terminal oxytocin fragments as well oxytocin(1-8) are formed by membrane-bound aminopeptidases and endopeptidases in vitro, respectively, the results suggest that, in addition to aminopeptidases, endopeptidase-like enzymes are involved in the proteolysis of endogenous brain oxytocin.
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PMID:Proteolytic conversion of oxytocin in vivo after microinjection in the rat hippocampus. 833 47

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.
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PMID:Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain. 902 55

1. Endothelin (ET) and its mRNA are present in endometrium. Expression of ET varies across the menstrual cycle, reaching maximal levels in the premenstrual phase, suggesting a paracrine role in endometrial bleeding and/or repair. 2. The major cellular source of ET is the epithelium, although endothelium and decidualized stroma are additional sites of production. Epithelial ET is the ET-1 isoform and this is able to contract rat thoracic aortic rings ex vivo. 3. Endothelin-1 production by cultured endometrial epithelial cells is markedly increased by serum and, to a lesser extent, by transforming growth factor-beta and interleukin-1 alpha, but not by epidermal growth factor, oxytocin, arginine vasopressin, thrombin or angiotensin II, which stimulate ET production in other tissues. 4. Endothelin-1 has mitogenic actions on endometrial stromal cells; it stimulates the uptake of [3H]-thymidine, acting via the AP-1 cis element c-jun. 5. Neutral endopeptidase (NEP), a membrane-bound ectoenzyme that is capable of degrading ET, is localized principally in endometrial stroma and immunoreactivity is maximal in the secretory phase of the cycle. 6. A potential role for ET in regulating endometrial bleeding is suggested by studies on endometrium from two groups of women who were experiencing abnormal uterine bleeding: users of the contraceptive Norplant (Leiras Co., Turku, Finland) and subjects with documented menorrhagia. In both groups, ET-1 immunoreactivity in endometrial epithelium was markedly reduced compared with the normal menstrual cycle and did not vary cyclically, while NEP immunoreactivity, particularly in the epithelium, was increased. Thus, ET may be involved in endometrial bleeding, as a vasoconstrictor before the onset of menstruation when vasoconstriction is intense and, subsequently, when it may be required in the cessation of menstrual bleeding. Furthermore, the mitogenic actions of ET may play a role in endometrial regeneration and remodelling during the menstrual cycle, particularly following menstruation.
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PMID:Endometrial endothelin: regulator of uterine bleeding and endometrial repair. 1006 38

A number of cytokines and their receptors are abundantly expressed at the materno-fetal interface and are thought to have a function in the regulation of placentation. Granulocyte-colony stimulating factor (G-CSF) is expressed by stromal cells in both placental tissue and maternal decidua throughout placentation. In this study, we examined the expression of placental G-CSF receptor (G-CSFR) mRNA and protein throughout gestation by ribonuclease protection assays, Western blotting, and immunohistochemistry. The major placental form of G-CSFR mRNA, corresponding to a membrane-bound form of the protein, was present in first-trimester placental tissues; levels decreased in second- and were highest in third-trimester placental tissues. Two placental G-CSFR molecules, 120 kDa and 150 kDa, were detected in first- and third-, but not second-, trimester tissues. The level of the 150-kDa G-CSFR was greater in the third- than in first-trimester samples. These differences were irrespective of whether or not the patients had received prostaglandin E1 analogues, prostaglandin E1 analogues and oxytocin, oxytocin alone, or mifepristone before labor. We demonstrated by immunohistochemistry that interstitial cytotrophoblast in first- and second-trimester decidual tissue and cytotrophoblast in term fetal membranes express G-CSFR. These data demonstrate that the expression of specific forms of placental G-CSFR is strictly cell type- and developmental stage-specific, and they suggest that G-CSFR may be important in decidual invasion of cytotrophoblast and in trophoblast function during placentation.
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PMID:Gestational regulation of granulocyte-colony stimulating factor receptor expression in the human placenta. 1008 50


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