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)

Magnocellular neurones in the supraoptic nucleus and paraventricular nucleus express mRNA for nitric oxide synthase (NOS) and the expression becomes more prominent when the release of vasopressin or oxytocin is stimulated. It has also been reported that NO donors inhibit the electrical activity of supraoptic nucleus neurones, but the mechanism involved in the inhibition remains unclear. In the present study, to know whether modulation of synaptic inputs into supraoptic neurones is involved in the inhibitory effect of NO, we measured spontaneous excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) from rat supraoptic nucleus neurones in slice preparations identified under a microscope using the whole-cell mode of the slice-patch-clamp technique. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), reversibly increased the frequency of spontaneous IPSCs mediated by GABAA receptors, without affecting the amplitude, indicating that NO potentiated IPSCs via a presynaptic mechanism. The NO scavenger, haemoglobin, suppressed the potentiation of IPSCs by SNAP. On the other hand, SNAP did not cause significant effects on EPSCs mediated by non-NMDA glutamate receptors. The membrane permeable analogue of cGMP, 8-bromo cGMP, caused a significant reduction in the frequency and amplitude of both IPSCs and EPSCs. The results suggest that NO preferentially potentiates the inhibitory synaptic inputs into supraoptic nucleus neurones by acting on GABA terminals in the supraoptic nucleus, possibly via a cGMP-independent mechanism. The potentiation may, at least in part, account for the inhibitory action of NO on the neural activity of supraoptic neurones.
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PMID:Preferential potentiation by nitric oxide of spontaneous inhibitory postsynaptic currents in rat supraoptic neurones. 1071 23

The subunit switching of ligand-gated receptors is a potentially important mechanism through which synaptic plasticity can be achieved in the nervous system. Although established in an activity-dependent manner for neurotransmission that is mediated by excitatory amino acids, there is much less direct evidence for a role of subunit switching in long-term plasticity of GABAA receptors in the adult. We argue that the hypothalamic oxytocin neurones, which exhibit marked plasticity through each reproductive cycle, provide an excellent model of both presynaptic and postsynaptic long-term plasticity of GABA-mediated transmission in the mature nervous system. The postsynaptic plasticity involves GABAA-receptor-subunit switching in an activity-independent manner. It also has profound effects on the electrical behaviour of the oxytocin neurones and, thus, the neural control of pregnancy and lactation.
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PMID:Long-term plasticity of postsynaptic GABAA-receptor function in the adult brain: insights from the oxytocin neurone. 1078 20

Marked plasticity in GABAA receptor signalling occurs in adult oxytocin neurons of the supraoptic nucleus (SON) through the modulation of GABAA receptor alpha subunits during pregnancy. The present studies were undertaken to examine the potential mechanisms underlying this plasticity. In vivo microdialysis experiments in conscious rats revealed that no significant changes in extracellular GABA concentrations occurred within the SON over the last two days of pregnancy and the time of parturition itself. In situ hybridization studies examined the effects of gonadal steroid manipulation upon the GABAA receptor subunits expressed by SON neurons (alpha1, alpha2, beta2 and gamma2 subunits) and demonstrated that cellular levels of the alpha1 subunit were increased following 8 days oestrogen and progesterone treatment. Estrogen alone or allopregnanolone, the progesterone derivative, had no effect on alpha1 subunit mRNA expression in the SON. Immunocytochemical experiments demonstrated progesterone receptors in many neural populations but not within the SON of late pregnant rats. These studies indicate that alterations in endogenous GABA release within the SON are unlikely to be responsible for the GABAA receptor plasticity exhibited by oxytocin neurons in late pregnancy. Rather, data demonstrate that the fluctuating concentrations of progesterone during pregnancy act indirectly on SON neurons to modulate alpha1 subunit mRNA expression. Together, these experiments provide evidence for the ligand-independent induction of GABAA receptor plasticity in the adult brain by progesterone.
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PMID:Progesterone regulation of GABAA receptor plasticity in adult rat supraoptic nucleus. 1079 39

The role of the dendrites of magnocellular neurones in the release of neurosecretory peptides and the synthesis of many proteins locally is reviewed. Oxytocin and vasopressin contained in dense-cored neurosecretory vesicles are released from magnocellular dendrites not only by excitatory transmitters such as glutamate acting through well-established receptors, but also by a rapid action of oestradiol acting by a mechanism which appears to involve NMDA receptors. Magnocellular dendrites also contain substantial amounts of the synthetic machinery which could synthesise proteins for local use. The presence in dendrites of polysomes and of mRNAs encoding microtubule-associated protein 2, calcium calmodulin kinase II, alpha-synapsin-associated protein, and components of the GABA(A) and NMDA receptors strongly suggests that these proteins can be translated in the dendrites, close to the sites at which they function. Mechanism(s) which control the translation of these dendritic mRNAs and the insertion into the dendritic membranes of proteins translated by dendritic ribosomes remain to be determined. However, an overall picture emerges of magnocellular dendrites as active secretory and synthetic components of the neurosecretory neurones.
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PMID:Dendritic secretion of peptides from hypothalamic magnocellular neurosecretory neurones: a local dynamic control system and its functions. 1079 15

The release of vasopressin and oxytocin is regulated by the electrical activity of magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei, which is under the control of a great variety of neurotransmitters and neuromodulators. The major neural signals to the supraoptic nucleus are from excitatory glutamate inputs and inhibitory GABA inputs. In recent studies, the voltage-clamp mode of the whole-cell patch-clamp technique has been applied to slice preparations from rat hypothalamus to monitor synaptic inputs to supraoptic neurones. Spontaneous excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) are abolished by CNQX and picrotoxin, respectively, but are insensitive to tetrodotoxin, indicating that they represent quantal release of glutamate and GABA, respectively, from nerve terminals of presynaptic neurones. GABA and glutamate show remarkable suppressive effects on both EPSCs and IPSCs via presynaptic GABA(B) and mGlu receptors, respectively. Noradrenaline, which excites supraoptic neurones via postsynaptic alpha1-receptors, also suppresses IPSCs and potentiates EPSCs. On the other hand, prostaglandin E2, which excites supraoptic neurones via postsynaptic prostaglandin E2 (EP) receptors of the EP4 subclass, also suppresses IPSCs via EP3 receptors but has little effect on EPSCs. Thus pre- and postsynaptic mechanisms may act cooperatively to excite supraoptic neurones. Nitric oxide, which inhibits supraoptic neurones, potentiates IPSCs without affecting EPSCs. This provides another example for the preferential modulation of IPSCs of supraoptic neurones. On the other hand, PACAP, which causes a long-lasting increase in the firing frequency via the postsynaptic receptors, has no effect on EPSCs and IPSCs, suggesting that some ligands act only at postsynaptic receptors. Thus multiple patterns for pre- and postsynaptic modulation are present in the supraoptic nucleus, and the electrical activity of supraoptic neurones is regulated via complex mechanisms at both pre- and postsynaptic sites.
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PMID:Pre- and postsynaptic modulation of the electrical activity of rat supraoptic neurones. 1079 17

The NT2 cell line, which was derived from a human teratocarcinoma, exhibits properties that are characteristic of a committed neuronal precursor at an early stage of development. NT2 cells can be induced by retinoic acid to differentiate in vitro into postmitotic central nervous system (CNS) neurons (NT2-N cells). The commitment of NT2-N cells to a stable neuronal phenotype is irreversible. Because it may be possible to transplant these human neurons to compensate for neuronal loss after traumatic injuries or neurodegenerative diseases of the CNS, knowledge of their phenotype is essential. This study aimed to characterize in detail the neurotransmission phenotype of NT2-N cells by using immunocytochemical methods. Single peroxidase immunostaining demonstrated that NT2-N cells expressed the gamma-aminobutyric acidergic (GABAergic), catecholaminergic, and cholinergic phenotypes to a large extent and expressed the serotonergic phenotype to a minor extent. NT2-N cells also expressed different neuropeptides, such as neuropeptide Y, oxytocin, vasopressin, calcitonin gene-related peptide, and Met- and Leu-enkephalin. Double fluorescence immunostaining further indicated that a large number of NT2-N cells could express GABA and another neurotransmitter or neuropeptide at the same time. Finally, electron microscopy demonstrated that these NT2 neurons elaborate classical synaptic contacts. The multipotentiality of these neurons, combined with their apparent functionality, suggests that they may represent useful material for a variety of therapeutic approaches aimed at replacing dead neurons after neurodegenerative diseases or lesions of the CNS.
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PMID:Human NT2 neurons express a large variety of neurotransmission phenotypes in vitro. 1086 14

Oxytocin (OT) modulation of synaptic transmission between olfactory bulb neurones has been implicated in the induction of maternal behaviour, but the mechanism of action is unknown. We examined the action of OT on gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in cultured mitral/tufted (M/T) cells with the use of whole-cell patch-clamp recordings. OT reversibly reduced the frequency of sIPSCs without affecting the amplitudes. The effect of OT on sIPSCs was mimicked by the OT receptor agonist [Thr(4), Gly(7)]-OT in a reversible manner and blocked by the OT receptor antagonist desGly-NH(2)(9), d(CH(2))(5)-[Tyr(Me)(2), Thr(4)]-ornithine-vasotocin. OT has no effect, however, on the membrane currents evoked by exogenous application of GABA. These results demonstrate that OT depresses GABA(A) receptor-mediated sIPSCs in M/T cells by a presynaptic mechanism.
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PMID:Oxytocin depresses spontaneous gamma-aminobutyric acid-ergic inhibitory postsynaptic currents in cultured mitral cells of the rat olfactory bulb by a presynaptic mechanism. 1089

The neural control of the subcommissural organ (SCO) has been partially characterized. The best known input is an important serotonergic innervation in the SCO of several mammals. In the rat, this innervation comes from raphe nuclei and appears to exert an inhibitory effect on the SCO activity. A GABAergic innervation has also been shown in the SCO of the rat and frog Rana perezi. In the rat, GABA and the enzyme glutamate decarboxylase are involved in the SCO innervation. GABA is taken up by some secretory ependymocytes and nerve terminals, coexisting with serotonin in a population of synaptic terminals. Dopamine, noradrenaline, and different neuropeptides such as LH-RH, vasopressin, vasotocin, oxytocin, mesotocin, substance P, alpha-neoendorphin, and galanin are also involved in SCO innervation. In the bovine SCO, an important number of fibers containing tyrosine hydroxylase are present, indicating that in this species dopamine and/or noradrenaline-containing fibers are an important neural input. In Rana perezi, a GABAergic innervation of pineal origin could explain the influence of light on the SCO secretory activity in frogs. A general conclusion is that the SCO cells receive neural inputs from different neurotransmitter systems. In addition, the possibility that neurotransmitters and neuropeptides present in the cerebrospinal fluid may also affect the SCO activity, is discussed.
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PMID:Neural input and neural control of the subcommissural organ. 1124 62

Understanding how neurons and glia sort and deliver cell adhesion molecules to their cell surface should provide important clues as to how such molecules participate in dynamic neuronal functions in the developing and adult brain. The present study examines translocation of polysialylated neural cell adhesion molecule (PSA-NCAM), a negative regulator of cell adhesion, in cells of the rat hypothalamo-neurohypophysial system in which it is expressed throughout life and which undergo morphological remodelling in response to stimulation. PSA-NCAM expression in this system does not vary markedly in relation to different conditions of regulated neurosecretion, suggesting that the glycoprotein reaches cell surfaces via the constitutive pathway. To study this more directly, we here used immunofluorescence for PSA on NCAM in live, unpermeabilized cells to monitor PSA-NCAM surface expression in organotypic slice cultures from postnatal rat hypothalami. Subsequent immunolabelling for oxytocin confirmed that the cultures included magnocellular oxytocinergic neurons displaying many properties of adult neurosecretory neurons in situ. In the cultures, immunoreaction for PSA-NCAM was visible on the surface of oxytocinergic and non-oxytocinergic axons. This reaction disappeared after exposure of the cultures to endoneuraminidase, an enzyme which specifically cleaves alpha-2-8-linked PSA from NCAM. PSA-NCAM reappeared on axonal surfaces 4h after enzyme washout. Such reexpression was visibly not affected by neuronal activity inhibition (blockade of Ca(2+) channels with Mn(2+), of Na(+) channels with tetrodotoxin, or of glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione or D-2-amino-5-phosphonopentanoic acid) or facilitation (K(+) depolarization or GABA-A receptor blockade with bicuculline). In contrast, PSA-NCAM surface translocation was inhibited reversibly by cooling the cultures at 20 degrees C, a procedure which blocks constitutive secretion and which resulted in accumulation of PSA-NCAM in the cytoplasm of oxytocinergic and non-oxytocinergic neurons. This treatment also revealed PSA-NCAM in the cytoplasm of underlying astrocytes. Our observations provide direct evidence that PSA-NCAM reaches the cell surface of hypothalamic neurons and astrocytes via the constitutive pathway, independently of Ca(2+) entry and enhanced neuronal activity. Thus, PSA-NCAM in the hypothalamo-neurohypophysial system would be continuously available to permit its cells to undergo remodelling whenever the proper stimulus intervenes.
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PMID:The polysialylated neural cell adhesion molecule reaches cell surfaces of hypothalamic neurons and astrocytes via the constitutive pathway. 1131 94

Histaminergic neurons of the tuberomammillary nucleus (TM) project monosynaptically to the supraoptic nucleus (SON). This projection remains intact in our hypothalamic slices and permits investigation of both brief synaptic responses and the effects of repetitively activating this pathway. SON oxytocin (OX) neurons respond to single TM stimuli with fast IPSPs, whose kinetics resemble those of GABA(A) or glycine receptors. IPSPs were blocked by the Cl(-) channel blocker picrotoxin, but not by bicuculline or strychnine, and by histamine H(2), but not by H(1) or H(3) receptor antagonists, suggesting the presence of an ionotropic histamine receptor and the possible nonspecificity of currently used H(2) antagonists. G-protein mediation of the IPSPs was ruled out using guanosine 5'-O-(2-thiodiphosphate) (GDP-betaS), pertussis toxin, and Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPs), none of which blocked evoked IPSPs. We also investigated the effects of synaptically released histamine on dye coupling and neuronal excitability. One hundred seventy-three OX neurons were Lucifer yellow-injected in horizontal slices. Repetitive TM stimulation (10 Hz, 5-10 min) reduced coupling, an effect blocked by H(2), but not by H(1) or H(3), receptor antagonists. Because H(2) receptors are linked to activation of adenylyl cyclase, TM-stimulated reduction in coupling was blocked by GDP-betaS, pertussis toxin, and Rp-cAMPs and was mimicked by 8-bromo-cAMP, 3-isobutyl-1-methylxanthine, and Sp-cAMP. Membrane potentials of OX and vasopressin neurons were hyperpolarized, accompanied by decreased conductances, in response to bath application of 8-bromo-cAMP but not the membrane-impermeable cAMP. These results suggest that synaptically released histamine, in addition to evoking fast IPSPs in OX cells, mediates a prolonged decrease in excitability and uncoupling of the neurons.
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PMID:Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling. 1131 81

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