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)

1. The central ganglia of a number of gastropod molluscs (including the marine snail Aplysia californica and the terrestrial snail Helix pomatia) contain neurones which exhibit endogenous patterns of oscillatory activity. 2. This oscillatory activity can be modulated for long periods of time by synaptic and hormonal stimulation. 3. Stimulation of appropriate pre-synaptic nerves causes long-lasting hyperpolarization in these neurones, with complete abolition of oscillatory activity. This synaptic response is mediated by an increase in K+ conductance, together with a decrease in inward (Na+/Ca2+) conductance. The ionic conductances affected by synaptic stimulation are those responsible for producing the rhythmic oscillations. 4. The oscillatory activity can also be modulated by the vertebrate neurohyophyseal peptides, vasopressin and oxytocin, and by an endogenous peptide-containing extract of molluscan ganglia. In contrast to synaptic stimulation, these agents cause an increase in oscillatory activity. 5. The endogenous molluscan factor which produces an increase in oscillatory activity can be purified by affinity chromatography on bovine neurophysin linked to Sepharose. This indicates that the molluscan nervous system may contain a neurohypophyseal-like peptide. 6. Oscillatory activity can be modulated by manipulation of cyclic nucleotide metabolism in these neurones. Increases in cAMP alone are associated with abolition of oscillatory activity; this mimics long-lasting synaptic hyperpolarization. Increases in cAMP and cGMP together are associated with an increase in oscillatory activity and mimic the effects of the vertebrate and molluscan peptides. Thus, it is possible that cyclic nucleotides play a role in these physiological responses.
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PMID:Synaptic and hormonal modulation of a neuronal oscillator: a search for molecular mechanisms. 51 75

The presence of a vasopressin (VP)- or vasotocin (VT)-like peptide in the central nervous system of the gastropod mollusc Aplysia has been indicated previously. In the case of Aplysia californica, HPLC and RIA evidence suggested the peptide was VT-like but not identical with the nonmammalian vertebrate peptide [Arg8]VT (AVT). In the present study, anterior ganglia extracts from the related species Aplysia kurodai were analyzed by HPLC followed by RIA. Further analysis of the major AVT-IR peak showed it to be indistinguishable, in three distinct solvent systems, from the sea snail venom peptide Lys-conopressin G, but to be different from the vertebrate peptides [Arg8]VP (AVP), [Lys8]VP (LVP), AVT, oxytocin (OT), mesotocin, isotocin, aspargtocin, glumitocin, and valitocin, from the sea snail venom peptide Arg-conopressin S, and from the peptides [Lys8]VT and [Gln8]OT. In addition, the carboxymethylated (CM) A. kurodai peptide had the same HPLC retention time as CM-Lys-conopressin G. The HPLC/RIA results suggest that (i) based on the properties of the solvent systems used, the A. kurodai peptide has two basic amino acids (like the conopressins but unlike the vertebrate peptides), and (ii) there is a high probability that the A. kurodai peptide is identical with Lys-conopressin G.
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PMID:A vasotocin-like peptide in Aplysia kurodai ganglia: HPLC and RIA evidence for its identity with Lys-conopressin G. 152 58

The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is localized in the lateral and medial hypothalamus and medial septum. The periaqueductal gray matter is a responsive site for mu receptor agonist- and neurotensin-induced inhibition of intestinal transit. The neural pathways from the brain to the gut whereby these peptides express their stimulatory or inhibitory effects on GI transit is vagal dependent with the exception of calcitonin. It is not known whether the vagally mediated inhibition of GI transit by these peptides results from a decrease activity of vagal preganglionic fibers synapsing with excitatory myenteric neurons or an activation of vagal preganglionic neurons synapsing with inhibitory myenteric neurons. The lack of specific antagonists for these peptides has hampered the assessment of their physiological role.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Central nervous system action of peptides to influence gastrointestinal motor function. 210 14

1. A phylogenetic study of oxytocin (OXT)-like immunoreactive cells was performed by the PAP method in the central nervous system of invertebrates. 2. The immunoreactivity was detected in the nerve cells of Hydra magnipapillata of the Coelenterata; Neanthes japonica and Pheretima communissima of the Annelida; Oncidium verrucosum, Limax marginatus and Meretrix lamarckii of the Mollusca; and Baratha brassica of the Arthropoda. 3. No immunoreactive cells were found in Bipalium sp. of the Platyhelminthes; Pomacea canaliculata, Aplysia kurodai, Bradybaena similaris and Achatina fulica of the Mollusca; and Gnorimosphaeroma rayi, Procambarus clarkii, Hemigrapsus sanguineus, Helice tridens and Gryllus bimaculatus of the Arthropoda; Asterina pectinifera of the Echinodermata; and Halocynthia roretzi of the Protochordata. 4. These results demonstrate that an OXT-immunoreactive substance is widely present not only in vertebrates but also in invertebrates. 5. OXT seems to have been introduced into these invertebrates at an early stage of their phylogenetic history.
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PMID:Phylogenetic study of the oxytocin-like immunoreactive system in invertebrates. 290 39

Attention is focused on the similarities in primary structure of the egg-laying neurohormone of the pulmonate Lymnaea stagnalis and of the opisthobranch Aplysia californica which both consist of 36 amino acid residues. FMRFamide-like peptides have now been isolated and sequenced from six molluscan species. Besides FMRFamide, two closely related peptides were isolated from the central nervous system of L. stagnalis and sequenced. This indicates that a family of FMRFamide-like peptides exist not only in the molluscs, but also within one species. A molluscan growth hormone, isolated from the brain of L. stagnalis, has been characterized. This small peptide hormone stimulates in vitro a receptor-adenylate cyclase system of mantle edge cells and in vivo the Ca2+-incorporation in the shell edge. The biochemical characterization of three vertebrate-like peptides of L. stagnalis, resembling oxytocin, Arg-vasopressin, and insulin, confirms the immunological findings that gastropods contain peptides which are structurally closely related to mammalian peptides.
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PMID:Molecular properties of various snail peptides from brain and gut. 391 18

Extracts of cerebral and pleuro-pedal ganglia from two terrestrial slugs, Ariolimax columbianus and Limax maximus, and from the marine opisthobranch, Aplysia californica, contain immunoreactivity resembling that of a vasotocin or vasopressin. Radioimmunoassays using several antisera indicate that the immunoreactivity is not due to vasotocin, vasopressin, or any other known naturally occurring neurohypophyseal peptide. Immunoreactivity of extracts on a relatively nonspecific vasopressin antiserum is well correlated with activity on antidiuretic assays on rats. Both immunoreactivity and antidiuretic activity are adsorbed onto bovine neurophysin affinity columns. Thus these extracts contain one or more peptides that closely resemble the vertebrate antidiuretic hormones, vasotocin and vasopressin, both immunologically and pharmacologically. The amounts of immunoreactivity and antidiuretic activity in ganglion extracts do not appear to change during dehydration and rehydration. Although both ganglionic extracts and vasotocin stimulate exudation of fluid across the slug body wall, the present experiments provide no evidence that the vasotocin-like material(s) in these ganglia may participate as neurotransmitters or hormones in the regulation of fluid balance. This remains an attractive hypothesis.
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PMID:Immunological and biological characteristics of the vasotocin-like activity in the head ganglia of gastropod molluscs. 672 97

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 purpose of this study was to determine the role of the axodendritic tree in the generation of bursting pacemaker activity in the identified Helix RPa1 neuron, which is homologous to the Aplysia R15 cell, and propagation of action potentials along the axons. In doing so, I used recording of RPa1 neuron electrical activity after cutting off the right or left parietovisceral connections, the two-electrode voltage-clamp technique, registration of electrical activity of visceral nerve containing RPa1 axon branches, isolation of the RPa1 neuron and puff application of oxytocin on it. Cutting of the right (but not left) parietovisceral connection in all cases (more than 15 preparations) evoked complete disappearance of bursting pacemaker activity in the RPa1 neuron and hyperpolarization of its membrane potential up to -65 to -67 mV. Such silent state of the RPa1 neuron was maintained after its complete isolation from the ganglion. The described cutting did not result in a change of bursting activity of the pacemaker neuron V7 located in the visceral ganglion, although isolation of the V7 neuron also eliminated its own activity. Puff application of oxytocin (10 microM in a micropipette) on to the RPa1 neuron both after cutting the right parietovisceral connection or isolation of the neuron from the ganglion resulted in all cases (more than 10 cells) in transient depolarization with development of beating, oscillatory or bursting activity. Voltage clamping of RPa1 soma in the intact ganglion at a level close to zero membrane current sometimes, and, as a rule, at a more depolarized level, revealed bursting-like oscillations of membrane current, reflecting electrical bursting activity in the unclamped remote region of a neuron, most likely in the dendritic tree. Voltage clamping of RPa1 soma possessing bursting activity reveals bursting-like oscillation of membrane current and prevents propagation of corresponding axon action potentials in the visceral nerve. Controversially, clamping of RPa1 soma possessing beating activity exhibits a beating-like oscillation of membrane current and does not prevent propagation of corresponding action potentials in the nerve. Within the framework of the developed hypothesis that persistent bursting pacemaker activity of the RPa1 neuron is due to a constant activation of its peptidergic synaptic inputs [Kononenko N. I. (1993) Comp. Biochem. Physiol. 106A, 135-147], the experimental results were interpreted in the manner that these synapses and, correspondingly, the locus of electrical bursting activity generation, are localized on the dendritic tree of the RPa1 neuron mainly or possibly exclusively in the visceral ganglion. It is hypothesized that bursting and beating neuronal activities are due to functioning of different loci of the dendritic tree, regarding their electrical relations with axon branches.
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PMID:Role of the axodendritic tree in the functioning of helix bursting neurons: generation of pacemaker activity and propagation of action potentials along the axon. 1068 80

The concept advanced by Berridge and colleagues that intracellular Ca(2+)-stores can be mobilized in an agonist-dependent and messenger (IP(3))-mediated manner has put Ca(2+)-mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca(2+)-stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP(3)) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.As cADPR and NAADP are structurally and functionally distinct, it is remarkable that they are synthesized by the same enzyme. They are thus fraternal twin messengers. We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and, through homology, found its mammalian homolog, CD38. Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion, susceptibility to bacterial infection, to social behavior of mice through modulating neuronal oxytocin secretion. We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis. This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.
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PMID:Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. 2178 93