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)

Our experiments with the neurophysin-related proteins from bovine NSG have demonstrated that these species differ in several important respects from the materials conventionally prepared. (1) In structural terms, the NSG proteins are essentially identical with the conventional neurophysins in amino acid composition and closely similar in immunoreactivity; however, the presence of carbodydrate and lipid moieties in the NSG material, no matter how they are attached, constitutes a structural difference apparently sufficient to cause considerable changes in properties. (2) The affinities for the neurohypophyseal hormones of the NSG proteins are very much higher than those of the "conventional" neurophysins and, moreover, the binding properties of the NSG material are much more stable with time under the conditions of the binding experiments. (3) The low binding capacities of the NSG materials, even when they are purified to apparent molecular homogeneity, indicate a functional heterogeneity perhaps related to supramolecular structure. (4) The conversion of the NSG proteins by acid or alkali treatment to materials resembling the "conventional" neurophysins in their binding properties suggests that the latter may be isolation artifacts. Although we cannot as yet consistently explain the properties of our neurophysins from NSG, we offer the hypothesis that the low binding capacity, as also the Hill coefficient greater than 1 (cf. Reference 25) are indicative of molecular aggregation, perhaps mediated or facilitated by the nonprotein components. It is conceivable that such aggregation, proceeding in the more "natural" environment of the NSG in a more precisely organized manner, might constitute the truly "native," fully functional state of the neurophysins. In this context it is of interest to record our preliminary observations, which suggest the presence of a protein of 10,000 mol. wt. in the NSG membrane fraction (SDS gel) as well as electron-microscopic indications30 of a highly organized ("crystalline") structure within these membranes. Although, therefore, the materials we have described may not merit the description of "native" neurophysins, we believe that they are certainly closer to the native state than the proteins conventionally isolated; and we would suggest that any discussion of the biological role of the neurophysins based on the properties of the conventional preparations may be at best speculative, and at worst misleading.
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PMID:Some properties of neurophysins isolated from bovine neurosecretory granules. 105 42

1. Earlier studies have shown that exposure of fat-cells to insulin results in the rapid increased phosphorylation of an acid-soluble 22 kDa protein and that increases in phosphorylation were also evident in cells exposed to adrenaline [Belsham & Denton (1980) Biochem. Soc. Trans. 8, 382-383; Belsham, Brownsey, Hughes & Denton (1980) Diabetologia 18, 307-312]. 2. The effects of adrenaline are shown to be brought about through beta-adrenergic receptors and to be mimicked by other agents which increase cell cyclic AMP concentrations. The maximum extent of phosphorylation is about 60% of that observed with insulin. Increased phosphorylation is also observed in fat-cells exposed to vasopressin, oxytocin and phorbol esters, but not to alpha-adrenergic agonists. 3. No changes in the phosphorylation of the protein are evident in epididymal fat-pads from fat-fed, starved or starved/refed animals, despite the large changes in protein composition of fat-cells which accompany these nutritional alterations. This suggests that the protein is not closely involved in lipogenesis or associated metabolic pathways, but rather that it may play a more general regulatory role. 4. The 22 kDa protein migrates as a doublet on SDS/PAGE even after purification to apparent homogeneity by sequential use of Mono Q chromatography, SDS/PAGE and h.p.l.c. The amino acid compositions of the two components are very similar and share features in common with a number of proteins, including inhibitor-1, inhibitor-2, dopamine- and cyclic-AMP-regulated phosphoprotein (DARPP-32), and G-substrate, which may be involved in the regulation of protein phosphatase activity. 5. Phosphopeptide mapping and phosphoamino acid analysis reveals that insulin increases the phosphorylation of two distinct peptides within the protein (in one peptide insulin increases the amount of phosphothreonine, whereas in the other the hormone increases the amounts of phosphothreonine and phosphoserine). Both components of the doublet exhibit similar changes in phosphorylation, and hence the differences in migration are not the result of differences in phosphorylation, as suggested previously [Blackshear, Nemenoff & Avruch (1983) Biochem. J. 214, 11-19]. The pattern of phosphorylation observed with the beta-adrenergic agonist isoprenaline was similar to that observed with insulin. 6. The possible role and regulation of the 22 kDa protein are discussed.
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PMID:Comparison of the effects of insulin and adrenergic agonists on the phosphorylation of an acid-soluble 22 kDa protein in rat epididymal fat-pads and isolated fat-cells. 134 72

The pre- and post-Golgi processing of preprovasopressin and prepro-oxytocin was evaluated by microsequencing for incorporated radiolabel. 35S-Cysteine and 3H-fucose were microinjected into rat supraoptic nuclei (SON), and proteins and peptides related to the biosynthesis of vasopressin (VP) and oxytocin (OT) were isolated at various times from the supraoptic nuclei and neural lobe by employing a one-step procedure of high performance liquid chromatography (HPLC). These proteins and peptides were recognized through their binding to specific antibodies against VP, OT, and rat neurophysins (RNPs), and by their binding to ConA-Sepharose. Two immunoreactive glycoproteins related to VP biosynthesis were recovered from the SON and both contained fucose and had a 35S-cysteine placement consistent with the location of the hormone sequence at the N-terminus. SDS-electrophoresis revealed the major protein form to be 21,000 daltons and the minor protein form to be 19,000 daltons. One nonglycosylated protein of 16,000 daltons related to oxytocin biosynthesis was recovered from the SON, and this protein also had a 35S-cysteine placement consistent with an N-terminal OT sequence. These data provide the first sequential evidence that prior to, or shortly after, packaging in the Golgi the preprohormones of VP and OT have lost their entire leader-peptide structures.
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PMID:Single-step isolation and sequencing of vasopressin and oxytocin precursors. 140 17

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
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PMID:Aminopeptidase P from human leukocytes. 144 89

Immunocytochemical and immunoblotting technique have been used to characterize the antigens recognized by two monoclonal antibodies (MAbs C6 and D5) produced against dissociated cells from punches of neonatal supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei of the rat. Peroxidase immunocytochemistry revealed that both MAbs label magnocellular perikarya in the adult and neonatal SON and PVN as well as smaller neurons in the suprachiasmatic nucleus. Axons of the hypothalamo-neurohypophysial tract are also immunolabeled within the hypothalamus and zona interna of the median eminence, and C6 and D5 each bind specifically to both the adult and neonatal neurohypophysis. Dual-label immunofluorescence experiments employing C6 or D5 simultaneously with rabbit antisera specific for either oxytocin, neurophysin or vasopressin neurophysin revealed that C6 binds only to vasopressinergic magnocellular perikarya in the SON, while D5 labels both vasopressinergic and a small subset of oxytocinergic magnocellular neurons. Post-embedding immunogold analysis of MAb binding to the neurohypophysis at the ultrastructural level showed that both C6 and D5 recognize antigens associated with large dense core neurosecretory granules in a subset of neurosecretory axons. Initial biochemical characterization of the antigens recognized by C6 and D5 was performed using SDS-PAGE and Western immunoblotting. MAbs C6 and D5 label single protein bands with apparent molecular weights of 38 and 68 kDa, resp., in blots of reduced extracts from the adult neurointermediate lobe. No cross-reactivity between C6 and D5 and the neurophysins was apparent, nor did anti-neurophysin sera recognize the bands identified by C6 and D5. We have therefore designated these novel antigens as VPGP38 and VPGP68 for VasoPressin Granule Proteins.
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PMID:Monoclonal antibodies identify two novel proteins associated with vasopressin secretory granules of the rat neurohypophysis. 186 40

The structural organization of small peptides reproducing the amino acid sequence of the common ocytocin/neurophysin precursor around the LysArg cleavage locus was investigated by a combination of spectroscopical techniques. In water both circular dichroism and [1H] NMR spectra indicated that these peptides adopted a random conformation. Evidence for folded structures was obtained when these compounds were placed in a membrane-like environment i.e. 40 mM SDS in phosphate buffer or trifluoroethanol. Whereas the CD spectra indicated the formation of various types of beta-turn in rapid equilibrium, measurements of NH temperature coefficients and Nuclear Overhauser Effects by 400 and 500 MHz NMR revealed the existence of contacts and of a folded conformation. These observations are discussed in relation with previous hypothesis made on the secondary structure organization of the proteolytic processing site of polypeptide hormone precursors.
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PMID:Evidence for beta-turn structure in model peptides reproducing pro-ocytocin/neurophysin proteolytic processing site. 213 68

Vasotocin-associated neurophysin (MSEL-neurophysin) has been purified from goose neurohypophysis through molecular sieving and high-pressure reverse-phase liquid chromatography (HPLC). The protein has a molecular mass (measured by SDS-polyacrylamide gel electrophoresis) of 17 kDa in contrast to 10 kDa found for the mammalian MSEL-neurophysins. Complete amino acid sequence (131 residues) has been determined mainly through tryptic or staphylococcal proteinase peptides derived from carboxyamidomethylated neurophysin, isolated by HPLC and microsequenced. N- and C-terminal sequences have been established by Edman degradation or action of carboxypeptidase Y, respectively, applied on the native protein. Goose MSEL-neurophysin is homologous to the two-domain "big" MSEL-neurophysin previously identified in the frog. It appears that in non-mammalian tetrapods, namely birds and amphibians, the proteolytic processing of the pro-vasotocin involves only one cleavage, releasing the hormone moiety and a "big" neurophysin with two domains homologous to mammalian MSEL-neurophysin and copeptin, respectively. Comparison of the avian protein with its mammalian and amphibian counterparts reveals that the first half of the polypeptide chain is evolutionarily much less variable than the second and that the goose protein resembles the frog protein much more than the mammalian one.
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PMID:Non-mammalian "big" neurophysins--complete amino acid sequence of a two-domain MSEL-neurophysin from goose. 227 53

The regional distribution of a novel pituitary protein (7B2) in the rat brain was studied using a specific and sensitive radioimmunoassay. Immunoreactive (IR)-7B2 was distributed throughout the brain, with the highest concentrations in the pituitary, hypothalamus and basal ganglia. Immunoreactive 7B2 from the brain and other tissues had an apparent molecular weight of around 20,000 as estimated by SDS-polyacrylamide gel electrophoresis as observed with other tissues. In homozygous Brattleboro rats which do not synthesize vasopressin or its associated neurophysin, IR-7B2 levels in the brain and pituitary gland were shown to be similar to those of control animals. Furthermore, the molecular weight of 7B2 in the brain and pituitary gland of homozygous Brattleboro rats was similar to that of control animals.
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PMID:Regional distribution of a novel pituitary protein (7B2) in the rat brain. 402 92

Neurophysins are part of the prohormones for vasopressin and oxytocin, and are localized with these hormones in the magnocellular cells of the neurohypophysis. New techniques have identified neurophysins in other areas within and outside the central nervous system, and we report here the isolation of neurophysins from the uterus of the rat. Using immunohistology the neurophysin immunoreactivity was localized to the epithelial lining cells of the uterus, and using radioimmunoassay was also present in uterine fluid suggesting secretion into the uterine cavity. The amount of uterine neurophysin increased in response to administered estrogen and was especially elevated in the pregnant uterus. The neurophysin-like material isolated from the uterus was similar to neurophysins from the neurohypophysis by radioimmunoassay, molecular sieve chromatography, isoelectric focusing and SDS gel electrophoresis. Both neurohypophyseal hormones, vasopressin and oxytocin, were also extracted from uterine endothelium and identified by radioimmunoassay and high pressure liquid chromatography.
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PMID:Isolation and localization of neurophysin-like proteins in rat uterus. 408 Jun 7

Biosynthesis, axoplasmic transport, and storage of neurophysin in the amphibian (Rana pipiens) magnocellular peptidergic neurosecretory system were studied, and the results were compared with those reported in mammals. After injection of [35S]cysteine into the preoptic recess, light microscopic autoradiography provides evidence that neurons of the preoptic nucleus (PON) synthesize cysteine-rich proteins. The time course of appearance of these [35S]cysteine-labeled proteins in different regions of the hypothalamo-neurohypophysial system was studied by slab gel autoradiography. [35S]Cysteine-labeled proteins were found in the PON less than 1 hr postinjection, whereas a major labeled protein, tentatively identified as the neurophysin, first appeared in the infundibulum and neural lobe 4 hr after the injection. In addition, the labeled neurophysin persisted in the neural lobe throughout the entire observation period of 5 days. The minimum transport rate for neurophysin was calculated as 0.9 mm/hr (22 mm/day) at 25 degrees C. Two different neurophysins (with isoelectric points (pI) 4.9 +/- 0.1, 4.6 +/- 0.1, and Mr = 23,000, 20,100) may be resolved from the neural lobe extracts by isoelectric focusing and SDS-polyacrylamide gel electrophoresis, respectively. In addition to the neurophysin peaks, two radioactive peaks with pI 5.2 and 5.8 may be detected in the preoptic nucleus and the infundibulum as early as 30 min after [35S]cysteine injection. Preliminary conversion studies suggest a putative precursor role for the pI 5.2 protein. The results indicate that in the amphibian peptidergic neurosecretory system, the synthesis of cysteine-rich neurophysin by the preoptic neurons, the transport through the infundibulum, and the storage in the neural lobe proceed similarily to their mammalian counterparts.
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PMID:Biosynthesis and axoplasmic transport of neurophysins in the hypothalamo-neurohypophysial system of Rana pipiens. 620 23


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