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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study modulatory actions of nitric oxide (NO) on GABAergic synaptic activity in hypothalamic magnocellular neurons in the supraoptic nucleus (SON), in vitro and in vivo electrophysiological recordings were obtained from identified oxytocin and vasopressin neurons. Whole cell patch-clamp recordings were obtained in vitro from immunochemically identified oxytocin and vasopressin neurons. GABAergic synaptic activity was assessed in vitro by measuring GABA(A) miniature inhibitory postsynaptic currents (mIPSCs). The NO donor and precursor sodium nitroprusside (SNP) and L-arginine, respectively, increased the frequency and amplitude of GABA(A) mIPSCs in both cell types (P < or = 0.001). Retrodialysis of SNP (50 mM) onto the SON in vivo inhibited the activity of both neuronal types (P < or = 0.002), an effect that was reduced by retrodialysis of the GABA(A)-receptor antagonist bicuculline (2 mM, P < or = 0.001). Neurons activated by intravenous infusion of 2 M NaCl were still strongly inhibited by SNP. These results suggest that NO inhibition of neuronal excitability in oxytocin and vasopressin neurons involves pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON.
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PMID:NO inhibits supraoptic oxytocin and vasopressin neurons via activation of GABAergic synaptic inputs. 1135 87

This issue of Peptides was inspired by a gathering of CCK researchers at the first Neuronal Cholecsytokinin Gordon Conference. The papers in this issue reflect the diversity of CCK research and demonstrate how the field has matured. Reviews describe the regulation of CCK gene expression and CCK release, the nature of the hormone binding site of the CCK A receptor, interaction of CCK, dopamine and GABA, the role of CCK in thermoregulation, sexual behavior and satiety in rodents and humans. The research articles document features of cardiovascular regulation, reduced cocaine sensitization and decreased satiety in rats that lack the CCK A receptor. Pro CCK processing in neuroblastoma cells and the elevation of CCK levels in CSF in a model of chronic pain are detailed in other articles. Three articles using different behavioral paradigms in rat and sheep examine CCK in learning and memory. Two articles that examine CCK in different behaviors that have a dopaminergic component are included. Other articles describe the interaction between a 5HT(3) antagonist and CCK-induced satiety and c-fos activation and document secretion of oxytocin and vasopressin in female patients and controls in response to CCK 4 administration. There is good reason to believe that the future is bright for research on CCK. With the organization of national and international meetings, CCK researchers have a forum for communication. Opportunities for cooperation and collaboration have never been better. The easy integration of academic basic and clinical science with industrial science bodes very well for the advancement of our understanding of the multiple roles that CCK plays in the brain and for the future development of CCK-based therapies.
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PMID:An introduction to neuronal cholecystokinin. 1145 11

How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.
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PMID:Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: an experimental and theoretical analysis. 1151 84

Both inhibitory GABAergic and excitatory glutamatergic inputs to supraoptic nucleus (SON) neurons can influence the release of vasopressin and oxytocin. Acetylcholine is known to excite SON neurons and to increase vasopressin release. The functional significance of cholinergic receptors, located at the presynaptic nerve terminals, in the regulation of the excitability of SON neurons is not fully known. In this study, we determined the role of presynaptic cholinergic receptors in regulation of the inhibitory GABAergic inputs to the SON neurons. The magnocellular neurons in the rat hypothalamic slice were identified microscopically, and the spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were recorded using the whole-cell voltage-clamp technique. The mIPSCs were abolished by the GABA(A) receptor antagonist, bicuculline (10 microM). Acetylcholine (100 microM) significantly reduced the frequency of mIPSCs of SON neurons from 3.59+/-0.36 to 1.62+/-0.20 Hz (n=37), but did not alter the amplitude and the decay time constant of mIPSCs. Furthermore, the nicotinic receptor antagonist, mecamylamine (10 microM, n=13), eliminated the inhibitory effect of acetylcholine on mIPSCs of SON neurons. The muscarinic receptor antagonist, atropine (100 microM), did not alter significantly the effect of acetylcholine on mIPSCs in most of the 17 SON neurons studied. These results suggest that the excitatory effect of acetylcholine on the SON neurons is mediated, at least in part, by inhibition of presynaptic GABA release. Activation of presynaptic nicotinic receptors located in the GABAergic terminals plays a major role in the cholinergic regulation of the inhibitory GABAergic input to SON neurons.
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PMID:Acetylcholine attenuates synaptic GABA release to supraoptic neurons through presynaptic nicotinic receptors. 1171 21

Brain slice preparations preserving projections from nearby forebrain cholinergic neurons to the supraoptic nucleus (SON) were used to study synaptic potentials mediated by nicotinic acetylcholine receptors (nAChRs) in the hypothalamus. Paired-pulse electrical stimulation in an area anterior to the SON that was rich in cholinergic cells confirmed the monosynaptic nature of the connections to putative oxytocin and vasopressin SON neurons. With ionotropic glutamate and GABA(A) transmission blocked, this stimulation evoked fast, atropine-insensitive EPSPs that were sensitive to nAChR antagonists. Evoked EPSPs were blocked by methyllycaconitine and alpha-bungarotoxin, antagonists that are selective for nAChRs containing the alpha7 subunit, but not by dihydro-beta-erythroidine at concentrations known to antagonize alpha4beta2 nAChRs. Although anatomical evidence exists for postsynaptic alpha4beta2 nAChRs in the SON, these results indicate that postsynaptic alpha7 nAChRs are primarily responsible for the cholinergically mediated EPSPs. Repetitive stimulation suggested partial desensitization of the receptors. With ionotropic glutamate transmission blocked, inhibition of AChE increased spontaneous EPSP frequency and amplitude, suggesting spontaneous ACh release. ACh, nicotine, and choline (a selective alpha7 nAChR agonist) were effective in evoking action potentials and repetitive firing with synaptic transmission blocked by low Ca2+, high Mg2+ medium. These agonists were also effective in evoking the type of phasic bursts characteristic of vasopressin neurons, long thought to be completely dependent on activation of NMDA receptors (NMDARs). Because phasic bursting is Ca2+-dependent, the functional equivalence of alpha7 nAChR and NMDAR activation in this regard is likely attributable to their large Ca2+ fluxing capacities. This is the first demonstration that synaptically released ACh results in fast, alpha7 nAChR-mediated EPSPs in hypothalamic neurons.
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PMID:Synaptic potentials mediated by alpha 7 nicotinic acetylcholine receptors in supraoptic nucleus. 1175 85

This review will focus on the activity of oxytocin neurons in the supraoptic nucleus (SON) and some factors that regulate their function during parturition and milk ejection in the rat. The level of oxytocin increases in the blood during parturition following a regression of the corpus luteum. The increase in oxytocin secretion is presumably a consequence of releasing the oxytocin neurons from restraining inhibitory influences of endogenous opioids-, nitric oxide-, and GABA-containing neurons following declining blood levels of progesterone on the one hand and increasing levels of estrogen on the other during late pregnancy. However, the principal stimulus for the increased oxytocin release is believed to originate, at least in part, from mechanical stimulation to the uterine cervix by fetuses near term, the resultant uterine contractile activity, and the fetal expulsion reflex. Hence, the contractile activity of the uterus acts through positive feedback mechanisms during parturition to stimulate oxytocin neurons as well, and this further increases the secretion of oxytocin. During suckling in lactating rats, somatosensory stimuli from the pups induce intermittent synchronized burst firing of oxytocin neurons, resulting in pulsatile increases in blood oxytocin concentrations to cause milk ejection. The oxytocin neurons appear to have an intrinsic capability to fire in a bursting fashion as determined by observation of this phenomenon in brain slice or tissue culture preparations. The release of oxytocin within the microenvironment of the SON and paraventricular nucleus coupled with morphological reorganization in these nuclei play important roles in the bursting activity of each oxytocin neuron and synchronization in vivo. However, the mechanism responsible for the synchronization of electrical activity in oxytocin neurons in the four discrete hypothalamic nuclei remains an interesting unanswered question.
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PMID:Role of the supraoptic nucleus in regulation of parturition and milk ejection revisited. 1181 Jul 14

Experiments were performed on freshly isolated dorsal root ganglion (DRG) neurons of rat. GABA(A)-activated currents were recorded using the whole-cell patch clamp technique. The majority of the neurons (48/52, 90.5%) were sensitive to GABA (10( 6)~10( 3) mol/L). Application of oxytocin (OT) induced outward membrane responses in 51.3% (20/39) of the neurons, no apparent responses in 43.6% (17/39) and inward responses in 5.1% (2/39). 10( 12), 10( 11), 10( 10) and 10( 9) mol/L OT increased 10( 4) mol/L GABA-activated currents to 24.1+/-7.6% (n=6), 33.4+/-6.9% (n=9), 40.2+/-6.5% (n=13) and 67.2+/-14.8% (n=5), respectively. After preapplication of OT, the Kd value for GABA(A)-activated currents decreased, while the response obtained at the maximum concentration increased. The results suggest that the enhancement of GABA-activated currents by OT may suppress primary sensory transmission by potentiating pre-synaptic inhibition of GABA.
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PMID:[Modulation of GABA-activated currents by oxytocin in rat dorsal root ganglion neurons]. 1194 91

Previous studies have shown that arginine vasopressin is an important neuropeptide that can modulate the reflex control of blood pressure and heart rate. The nucleus ambiguus, where cardiac parasympathetic neurons are located, receives dense arginine vasopressin projections. However the mechanisms by which arginine vasopressin alters cardiac parasympathetic activity are unknown. We tested the hypothesis that arginine vasopressin can alter the activity of cardiac parasympathetic neurons by altering the spontaneous GABAergic input to these neurons. Experiments were conducted using whole cell patch clamp recordings of cardiac parasympathetic neurons in an in vitro slice preparation in rats. The results of this study demonstrate that arginine vasopressin increases the frequency and amplitude of GABAergic inhibitory post-synaptic currents in cardiac parasympathetic neurons. Arginine vasopressin did not alter the GABAergic currents evoked by exogenous application of GABA. Similarly, in the presence of tetrodotoxin, arginine vasopressin did not alter the frequency, amplitude or decay time of GABAergic miniature synaptic events evoked by high osmolarity. These results indicate that arginine vasopressin likely acts on neurons precedent to cardiac parasympathetic neurons and that arginine vasopressin likely acts not at the synaptic terminal but at the soma or dendrites of the precedent neuron. Oxytocin and agonists for the V(2)-arginine vasopressin and V(1b)-arginine vasopressin receptors had no effect. By contrast, the arginine vasopressin-evoked responses were completely abolished by a selective V(1a)-arginine vasopressin receptor antagonist indicating arginine vasopressin responses are mediated by V(1a)-arginine vasopressin receptors. We conclude that the V(1a)-arginine vasopressin receptor-mediated increase in frequency and amplitude of inhibitory GABAergic activity to cardiac parasympathetic neurons may be at least one mechanism by which central arginine vasopressin may increase heart rate and inhibit reflex bradycardia.
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PMID:Arginine vasopressin enhances GABAergic inhibition of cardiac parasympathetic neurons in the nucleus ambiguus. 1203 55

The parenchymal cells of the mammalian pineal gland are the hormone-producing pinealocytes and the interstitial cells. In addition, perivascular phagocytes are present. The phagocytes share antigenic properties with microglial and antigen-presenting cells. In certain species, the pineal gland also contains neurons and/or neuron-like peptidergic cells. The peptidergic cells might influence the pinealocyte by a paracrine secretion of the peptide. Nerve fibers innervating the mammalian pineal gland originate from perikarya located in the sympathetic superior cervical ganglion and the parasympathetic sphenopalatine and otic ganglia. The sympathetic nerve fibers contain norepinephrine and neuropeptide Y as neurotransmitters. The parasympathetic nerve fibers contain vasoactive intestinal peptide and peptide histidine isoleucine. Recently, neurons in the trigeminal ganglion, containing substance P, calcitonin gene-related peptide, and pituitary adenylate cyclase-activating peptide, have been shown to project to the mammalian pineal gland. Finally, nerve fibers originating from perikarya located in the brain containing, for example, GABA, orexin, serotonin, histamine, oxytocin, and vasopressin innervate the pineal gland directly via the pineal stalk. Biochemical studies have demonstrated numerous receptors on the pinealocyte cell membrane, which are able to bind the neurotransmitters located in the pinealopetal nerve fibers. These findings indicate that the mammalian pinealocyte can be influenced by a plethora of neurotransmitters.
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PMID:The anatomy and innervation of the mammalian pineal gland. 1211 44

It is now generally accepted that magnocellular neurons of the supraoptic and paraventricular nuclei release the neuropeptides oxytocin and vasopressin from their dendrites. Peptide release from their axon terminals in the posterior pituitary and dendrites differ in dynamics suggesting that they may be independently regulated. The dendritic release of peptide within the supraoptic nucleus (SON) is an important part of its physiological function since the local peptides can regulate the electrical activity of magnocellular neurons (MCNs) which possess receptors for these peptides. This direct postsynaptic action would affect the output of peptide in the neurohypophysis. Another way that these peptides can regulate MCN activity would be to modulate afferent inputs unto themselves. Although the influence of afferent inputs (inhibitory and excitatory) on SON magnocellular neuron physiology has been extensively described in the last decade, a role for these locally released peptides on synaptic physiology of this nucleus has been difficult to show until recently, partly because of the difficulty of performing stable synaptic recordings from these cells in suitable preparations that permit extensive examination. We recently showed that under appropriate conditions, oxytocin acts as a retrograde transmitter in the SON. Oxytocin, released from the dendrites of MCNs, decreased evoked excitatory synaptic transmission by inhibiting glutamate release from the presynaptic terminals. It modulated voltage-dependent calcium channels, mainly N-type and to a lesser extent P/Q-type channels, located on glutamatergic terminals. Although evidence is less conclusive, it is possible that vasopressin has similar actions to reduce excitatory transmission. This synaptic depressant effect of oxytocin and/or vasopressin, released from dendrites, would ensure that MCNs regulate afferent input unto themselves using their own firing rate as a gauge. Alternatively, it may only be a subset of afferent terminals that are sensitive to these peptides, thereby providing a means for the MCNs to selectively filter their afferent inputs. Indeed its specificity is partly proven by our observation that oxytocin does not affect spontaneous glutamate release, or GABA release from inhibitory terminals (Brussaard et al., 1996). Thus, the dendrites of MCNs of the supraoptic nucleus serve a dual role as both recipients of afferent input and regulators of the magnitude of afferent input, allowing them to directly participate in the shaping of their output. This adds to a rapidly growing body of evidence in support of the concept of a two-way communication between presynaptic terminals and postsynaptic dendrites, and shows the potential of this nucleus as a model to study such form of synaptic transmission.
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PMID:Modulation of synaptic transmission by oxytocin and vasopressin in the supraoptic nucleus. 1243 39


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