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 interaction of bromophenol blue and related dyes with bovine neurophysin-I was studied by equilibrium dialysis and gel filtration, absorption and circular dichroism spectroscopy, and analytical ultracentrifugation. Binding isotherms for bromophenol blue showed positive cooperativity, with one strong site and one or more weaker sites present per polypeptide chain at pH 4 and an apparent increase in relative importance of the weaker sites of lower pH. Circular dichroism (CD) studies suggested displacement of bound dye by peptides that bind to the neurophysin hormone binding site. Titration of bound bromophenol blue indicated that the deprotonated dye was bound to the strong site with approximately 20-fold greater affinity than the protonated dye. The pH dependence of binding of bromophenol blue and of bromocresol purple, which has a higher pKa than bromophenol blue, indicated that binding was dependent on protonation of a protein residue with a pKa of 2.9. This residue was identified as a protein carboxyl, probably on an abnormal side chain, by studies of glycine ethyl ester modified neurophysin and carboxypeptidase-treated neurophysin. The presence of exciton interactions between bound dye molecules when only one dye was bound per polypeptide chain and analytical ultracentrifugation results indicated that dye was bound predominantly to the dimeric form of the protein. The implication of the data are discussed with respect to a kinetic model of dye-neurophysin interaction, used elsewhere in a study of neurophysin dimerization, that assumed interaction of protein monomers with protonated dye. Additionally, results are presented which suggest, in disagreement with conclusions based on the kinetic model, that there is a pH-dependent component of neurophysin dimerization which parallels low pH fluorescence and CD changes observed earlier.
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PMID:Interaction of bromophenol blue and related dyes with bovine neurophysin-I: use as a probe of neurophysin chemistry. 729 64

Recent observations indicate that the rat ovary receives not only adrenergic but also peptidergic innervation. In ruminants, there are few data available on the extent of a possible direct regulation of the peptidergic innervation of the ovary including the corpus luteum (CL). The direct effects of neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal polypeptide (VIP) on the release of progesterone and oxytocin from midluteal phase CL (days 8-12) were examined in vitro. A possible direct neural influence might provide a sensitive short-term control. Long-term as well as short-term effects were assessed using both a serum-reduced luteal cell culture and a microdialysis system (MDS) of luteal tissue. In the long-term experiments, luteal cells were preincubated from the start of the culture for 48 h with NPY, SP and VIP (10 pmol/1-100 nmol/l). During the following 4 h the neuropeptides showed a dose-dependent stimulation of progesterone release, but there was no effect on oxytocin release. LH showed a synergistic effect with NPY, SP and VIP on progesterone release. In the short-term experiments, the neuropeptides were added 48 h after the start of the culture. All three peptides were most stimulatory to LH-supported progesterone release 30 min after addition, and the effect decreased greatly thereafter to the control level from 60 to 120 min. In contrast, LH alone induced the maximal progesterone stimulation at 120 min. In the MDS, a 30-min perfusion with NPY, SP or VIP (10 nmol/l, 100 nmol/l and 1 mumol/l) induced significant acute effects on progesterone and oxytocin release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple effects of neuropeptide Y, substance P and vasoactive intestinal polypeptide on progesterone and oxytocin release from bovine corpus luteum in vitro. 750 90

Neuronal peptides exert neurohormonal and neurotransmitter (neuromodulator) functions in the central nervous system (CNS). Besides these functions, a group of neuropeptides may have a capacity to create cell proliferation, growth, and survival. Axotomy induces transient (1-21 d) upregulation of synthesis and gene expression of neuropeptides, such as galanin, corticotropin releasing factor, dynorphin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, cholecystokinin, angiotensin II, and neuropeptide Y. These neuropeptides are colocalized with "classic" neurotransmitters (acetylcholine, aspartate, glutamate) or neurohormones (vasopressin, oxytocin) that are downregulated by axotomy in the same neuronal cells. It is more likely that neuronal cells, in response to axotomy, increase expression of neuropeptides that promote their survival and regeneration, and may downregulate substances related to their transmitter or secretory activities.
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PMID:Neuropeptide messenger plasticity in the CNS neurons following axotomy. 757 12

A cDNA encoding a receptor for the oxytocin-related peptide isotocin has been identified by screening a lambda gt11 library constructed from poly(A)+ RNA of the hypothalamic region of the teleost Catostomus commersoni. The probe used was obtained by PCR amplification of white sucker genomic DNA using degenerate primers based on conserved sequences in the mammalian receptor counterparts. The full-length cDNA specifies a polypeptide of 390 amino acid residues that displays the typical hydrophobicity profile of a seven transmembrane domain receptor and which exhibits greatest similarity to mammalian oxytocin receptors. Oocytes that express the cloned receptor respond to the application of isotocin by an induction of membrane chloride currents indicating that it is coupled to the inositol phosphate/calcium pathway. The isotocin receptor (ITR) can also be activated by vasotocin, mesotocin, oxytocin and Arg-vasopressin, although these have lower potencies than isotocin. ITR-encoding mRNA has been detected in brain, intestine, bladder, skeletal muscle, lateral line, gills and kidney indicating that this receptor may mediate a variety of physiological functions.
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PMID:Teleost isotocin receptor: structure, functional expression, mRNA distribution and phylogeny. 765 82

The present study aimed to check the hypothesis concerning the monoamine regulation of the differentiation of their target neurons during ontogenesis. For this aim, neuropeptide gene expression has been evaluated by in situ hybridization in targets for monoamines, differentiating peptidergic neurons, after monoamine depletion in rats during prenatal or early postnatal periods. In the first series of experiments, the vasopressin (VP) and oxytocin (OT) mRNA concentrations were measured in the supraoptic nucleus (SON) of rat fetuses at the 21st embryonic day (E21) following daily (E13-E20) treatment with the inhibitor of the catecholamine (CA) synthesis, alpha-methyl-m(p)-tyrosine. Similar study was performed with rats at the 11th postnatal day (P11) after daily (P2-P10) treatment with alpha-methyl-m-tyrosine and the neurotoxin, 6-hydroxydopamine. In the second series of experiments, the effect of serotonin (5-HT) depletion by the inhibitor of the 5-HT synthesis, p-chlorophenylalanine, on the vasoactive intestinal polypeptide (VIP) mRNA level in the suprachiasmatic nucleus (SCN) has been studied in fetuses and in neonates as described above. No changes were detected in the VP and OT mRNA concentration in the SON following CA depletion in fetuses, while similar treatment of neonates significantly increased both mRNA levels. On the contrary, the 5-HT depletion caused an increased VIP mRNA concentration in the SCN in fetuses but not in neonates. Thus, our data suggest a monoamine inhibitory influence on peptide gene expression in the differentiating target neurons during certain periods of ontogenesis.
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PMID:Monoamine influence on neuropeptide gene expression during ontogenesis. 772 32

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

Targeted tumorigenesis, using the POMC gene promoter ligated to the simian virus 40 large T antigen, generated transgenic mice with massive tumors of the intermediate lobe (IL) of the pituitary. Inoculation of nude mice with the IL tumor cells resulted in very large secondary tumors. As the IL from several species produces a potent PRL-releasing factor (PRF), it was of interest to determine whether IL tumors from these mice also contain PRF. The objectives were to 1) measure serum PRL levels in mice with IL tumors, 2) determine whether these tumors contain PRF and examine its chromatographic properties, and 3) analyze whether this PRF is related to POMC, its derivatives, or other PRL secretagogues. Serum PRL levels were 5- to 6-fold higher in transgenic than in control mice. Primary and secondary IL tumors were acid extracted and successively fractionated using Sephadex G-100 gel filtration and reverse phase and gel permeation HPLC. PRF activity was determined using short term incubation of tissue extracts or column fractions with GH3 cells. Crude tumor extracts exhibited a strong and dose-dependent PRF activity. Upon chromatography, the PRF activity from either primary or secondary tumors resolved into two classes of compounds: a big PRF with an estimated mol wt of 70-80 kilodaltons and two small, very hydrophobic peptides. The elution profiles of the three PRFs differed from those of beta-endorphin, alpha MSH, beta MSH, ACTH, TRH, oxytocin, angiotensin II, vasoactive intestinal polypeptide, or corticotropin-like intermediate peptide. In summary, we have identified an animal model with IL tumors that has hyperprolactinemia and overproduces PRF. Two classes of PRFs, big and small, were resolved which differ from POMC derivatives and known regulators of PRL release. These data suggest that PRF is produced by melanotrophs, but is not a product of the POMC gene. The IL tumors should provide an excellent source for the purification and structural elucidation of PRFs.
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PMID:Identification of two classes of prolactin-releasing factors in intermediate lobe tumors from transgenic mice. 778 36

The R15 neuropeptides have been identified in the marine mollusc Aplysia californica. They compose a new family of neuropeptides acting on the cardiovascular, digestive, respiratory, reproductive and nervous systems. In this report we show that one of the members of the R15 neuropeptide family, the alpha 2 peptide is conserved in lower mammals. We have identified R15 alpha 2 immunoreactive neurons in the neurosecretory cell groups of the hypothalamus and in the brainstem of the hedgehog (Erinaceus europaeus). The majority of labeled cells were localized to the anterior periventricular part of the paraventricular nucleus and the accessory neurosecretory cell groups in the lateral hypothalamus as well as to the dorsal part of the nucleus tractus solitarii. In the paraventricular nucleus, R15 alpha 2 immunoreactive neurons also exhibit immunoreactivity for oxytocin, corticotropin releasing factor, vasoactive intestinal polypeptide and for the FMRFamide-related peptide which we found to be conserved in the hedgehog brain as well. No complete colocalization of R15 alpha 2 with any of the neuroactive substances tested, is observed. The highest degree of coexistence occurs with FMRFamide-related peptide, followed by vasoactive intestinal polypeptide, oxytocin and corticotropin releasing factor.
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PMID:Localization of molluscan R15 alpha 2 peptide immunoreactivity in the mammalian brain. 795 93

The retinal innervation, cytoarchitectural, and immunohistochemical organization of the suprachiasmatic nucleus (SCN) was studied in the domestic sheep. The SCN is a large elongated nucleus extending rostrocaudally for roughly 3 mm in the hypothalamus. The morphology is unusual in that the rostral part of the nucleus extends out of the main mass of the hypothalamus onto the dorsal aspect of the optic chiasm. Following intraocular injection of wheat-germ agglutinin-horseradish peroxidase or tritiated amino acids, anterograde label is distributed throughout the SCN. Retinal innervation of the SCN is bilaterally symmetric or predominantly ipsilateral. Quantitative image analysis demonstrates that, although the amount of autoradiographic label is greatest in the ventral and central parts of the nucleus, density varies progressively between different regions. In addition to the SCN, retinal fibers are also seen in the medial preoptic area, the anterior and lateral hypothalamic area, the dorsomedial hypothalamus, the retrochiasmatic area, and the basal telencephalon. Whereas the SCN can be identified using several techniques, complete delineation of the nucleus requires combined tract tracing, cytoarchitectural, and histochemical criteria. Compared with the surrounding hypothalamic regions, the SCN contains smaller, more densely packed neurons, and is largely devoid of myelinated fibers. Cell soma sizes are smaller in the ventral SCN than in the dorsal or lateral parts, but an obvious regional transition is lacking. Using Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining, the SCN can be clearly distinguished in the rostral and medial regions, but is less differentiated toward the caudal pole. Immunohistochemical demonstration of several neuropeptides shows that the neurochemical organization of the sheep SCN is heterogeneous, but that it lacks a distinct compartmental organization. Populations of different neuropeptide-containing cells are found throughout the nucleus, although perikarya positive for vasoactive intestinal polypeptide and fibers labeled for methionine-enkephalin are predominant ventrally; neurophysin-immunoreactive cells are more prominent in the dorsal region and toward the caudal pole. The results suggest that the intrinsic organization of the sheep SCN is characterized by gradual regional transitions between different zones.
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PMID:The suprachiasmatic nucleus in the sheep: retinal projections and cytoarchitectural organization. 795 5

The aim of this study was to investigate the role of vagal nerve activity for the release of oxytocin, prolactin and gastrointestinal (GI) hormones during suckling as well as for the secretion of milk in lactating rats. We have therefore performed experiments on vagotomized lactating rats. The animals were decapitated and trunk blood was collected from nonsuckling rats and from suckling rats in connection with milk ejection. Oxytocin, prolactin, vasoactive intestinal polypeptide (VIP), somatostatin, insulin, glucagon and glucose levels in plasma were measured by RIA-technique. In addition, maternal weight as well as the weight of the litters were recorded 7 d after vagotomy. As expected, oxytocin and prolactin levels rose in response to suckling in sham-operated controls. In vagotomized animals the suckling-induced increase of oxytocin was blocked and prolactin levels were significantly decreased. VIP levels in plasma increased following suckling in sham-operated animals and failed to respond after vagotomy. In contrast, somatostatin levels that rose significantly in sham-operated rats were even more significantly raised in vagotomized animals. In addition, insulin but not glucagon levels were increased by suckling. The insulin response, however, persisted after vagotomy. Interestingly, suckling was followed by a lowering of blood-glucose levels in vagotomized, but not in sham-operated animals. The vagotomized rats ate as much and increased in weight as sham-operated rats during the 7 d of vagotomy. The litters of vagotomized rats, however, gained significantly less weight in comparison with control litters. In conclusion, this study shows that vagal nerve activity is of importance for the release of oxytocin, prolactin, vasoactive intestinal polypeptide and somatostatin during suckling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of vagal nerve activity during suckling. Effects on plasma levels of oxytocin, prolactin, VIP, somatostatin, insulin, glucagon, glucose and of milk secretion in lactating rats. 797 18


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