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

The interactions of the dendritically released neuropeptides vasopressin and oxytocin with co-released neuroactive substances such as opioids and nitric oxide are reviewed. Endogenous opioids regulate magnocellular neurons at the level of the supraoptic nucleus and the relationship of dendritically released peptides and co-released opioids seems to be dependent on the stimulus given and the physiological state of the animal. Nitric oxide has a prominent inhibitory action on supraoptic neurons and these actions are predominantly mediated indirectly by GABA inputs. The role of these co-released neuroactive substances in differentially regulated release of neuropeptides from dendrites versus distant axon terminals has to be determined in more detail. A picture emerges in which release of vasopressin and oxytocin from different anatomical compartments of a single neuron may arise from different intracellular secretory pools and their preparation before release.
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PMID:The active role of dendrites in the regulation of magnocellular neurosecretory cell behavior. 1243 40

A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by GABA and GABA agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of oxytocinergic neurons in the paraventricular nucleus by dopamine, oxytocin and excitatory amino acids is apparently secondary to the activation of nitric oxide (NO) synthase. NO in turn activates, by a mechanism that is as yet unidentified, the release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas. Several peptide analogues of hexarelin, a growth hormone releasing peptide, also induce penile erection when injected into the paraventricular nucleus and, to a lesser extent, systemically, apparently by acting on a specific receptor to activate oxytocinergic neurons as shown for the above drugs and oxytocin. Paraventricular oxytocinergic neurons and mechanisms similar to those reported above are also involved in the expression of penile erection in physiological contexts, namely when penile erection is induced in the male by the presence of an inaccessible receptive female, which is considered a model for psychogenic impotence in man, as well as during copulation. These findings show that paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas and to the spinal cord are a likely target for the treatment of erectile dysfunction of central origin.
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PMID:Central oxytocinergic neurotransmission: a drug target for the therapy of psychogenic erectile dysfunction. 1252 90

YAWNING IS A COMMON PHYSIOLOGICAL EVENT THAT CAN BE DIVIDED INTO THREE DISTINCT PHASES: a long inspiratory phase, a brief acme and a rapid expiration. The aim of yawning is not yet well defined. However this semi-voluntary event increases vigilance and aims to alert when drowsiness occurs. Yawning probably has an important role for social communication as well. Yawning can be responsible for pain, luxation or even transient ischaemic attack. Abnormal yawning is present in various pathologies: migraine, Parkinson's disease, tumours, psychiatric diseases, infections or iatrogenic pathologies. The neuro-pharmacology of yawning is complex and knowledge of its mechanisms is incomplete. While under the control of several neurotransmitters, yawning is largely affected by dopamine. Dopamine may activate oxytocin production in the paraventricular nucleus of the hypothalamus. Oxytocin may then activate cholinergic transmission in the hippocampus and, finally, acetylcholine might induce yawning via the muscarinic receptors of the effectors. This is an over-simplification; many other molecules can modulate yawning, such as nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opium derivate peptides. Dopamine involvement in yawning could have practical applications in the study of new drugs or the exploration of neurological diseases such as migraine or psychosis. 2001 Harcourt Publishers Ltd
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PMID:Yawning. 1253 Sep 94

In this study, we investigate how neurosteroid sensitivity of GABA(A) receptors (GABA(A)Rs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA(A)Rs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABA(A)Rs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABA(A)Rs from a neurosteroid-sensitive mode toward a condition in which the receptors are not sensitive. This indicates that there may be an inverse causal relationship between the extent to which the GABA(A)R or one of its interacting proteins is phosphorylated and the neurosteroid sensitivity of the GABA(A)R. Neurosteroid sensitivity was not affected by changes in subunit composition of GABA(A)Rs known to occur concurrently in these cells.
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PMID:Oxytocin regulates neurosteroid modulation of GABA(A) receptors in supraoptic nucleus around parturition. 1257 7

Nitric oxide (NO) is known to regulate the release of arginine-vasopressin (AVP) and oxytocin (OT) by the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). The aim of the current study was to identify in these nuclei the NO-producing neurons and the NO-receptive cells in mice. The determination of NO-synthesizing neurons was performed by double immunohistochemistry for the neuronal form of NO synthase (NOS), and AVP or OT. Besides, we visualized the NO-receptive cells by detecting cyclic GMP (cGMP), the major second messenger for NO, by immunohistochemistry on hypothalamus slices. Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice. By contrast, cGMP was not observed in magnocellular neurons, but in GABA-, tyrosine hydroxylase- and glutamate-positive fibers, as well as in GFAP-stained cells. The cGMP-immunostaining was abolished by incubating brain slices with a NOS inhibitor (L-NAME). Consequently, we provide the first evidence that NO could regulate the release of AVP and OT indirectly by modulating the activity of the main afferents to magnocellular neurons rather than by acting directly on magnocellular neurons. Moreover, both the NADPH-diaphorase activity and the mean intensity of cGMP-immunofluorescence were increased in monoamine oxidase A knock-out mice (Tg8) compared to control mice (C3H) in both nuclei. This suggests that monoamines could enhance the production of NO, contributing by this way to the fine regulation of AVP and OT release and synthesis.
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PMID:The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathways. 1258 Nov 64

In adult rats somato-dendritic release of oxytocin and vasopressin from magnocellular neurones in the supraoptic nucleus of the hypothalamus has important autoregulatory actions on the neuronal electrical activity, and in neonatal rats it plays a role in the development of dendritic arborisation. In the adult, oxytocin effects are modulated by allopregnanolone via an interaction with inhibitory GABAA receptors. This study examined the effects of allopregnanolone, progesterone and 17beta-oestradiol on oxytocin and vasopressin release from intact isolated supraoptic nuclei and from the neurophypophyses in rats of differing ages. In supraoptic nuclei from rats of 3-4 weeks old or less, all three neurosteroids induced oxytocin release from the isolated supraoptic nucleus, but only allopregnanolone induced significant release of vasopressin. Surprisingly, in these very young rats, allopregnanolone-induced oxytocin release was inhibited by GABAA receptor antagonists as well as by an oxytocin receptor antagonist. By contrast, in supraoptic nuclei from adult rats allopregnanolone-induced oxytocin release was much smaller, and was enhanced in the presence of bicuculline. The GABAA receptor agonist muscimol also induced oxytocin release from supraoptic nuclei in young rats, but had no effect in adult rats. Oxytocin cells isolated from young rats showed an increase in [Ca2+]i in response to both allopregnanolone and muscimol. Allopregnanolone had no effect on [Ca2+]i or on the release of oxytocin or vasopressin from neurohypophysial axon terminals in either young or old rats. We conclude that, in very young rats, (i) neurosteroids induce oxytocin release from the supraoptic nucleus by a mechanism that partly depends on the presence of GABA, which in young rats is depolarising to oxytocin cells, and which also partly depends upon endogenous oxytocin, and (ii) the effect of allopregnanolone upon oxytocin release changes with age, as the functional activity of GABAA receptors changes from excitation to inhibition of oxytocin cells.
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PMID:Neurosteroid regulation of oxytocin and vasopressin release from the rat supraoptic nucleus. 1258 1

Oxytocin secretion from the posterior pituitary gland is increased during parturition, stimulated by the uterine contractions that forcefully expel the fetuses. Since oxytocin stimulates further contractions of the uterus, which is exquisitely sensitive to oxytocin at the end of pregnancy, a positive feedback loop is activated. The neural pathway that drives oxytocin neurons via a brainstem relay has been partially characterised, and involves A2 noradrenergic cells in the brainstem. Until close to term the responsiveness of oxytocin neurons is restrained by neuroactive steroid metabolites of progesterone that potentiate GABA inhibitory mechanisms. As parturition approaches, and this inhibition fades as progesterone secretion collapses, a central opioid inhibitory mechanism is activated that restrains the excitation of oxytocin cells by brainstem inputs. This opioid restraint is the predominant damper of oxytocin cells before and during parturition, limiting stimulation by extraneous stimuli, and perhaps facilitating optimal spacing of births and economical use of the store of oxytocin accumulated during pregnancy. During parturition, oxytocin cells increase their basal activity, and hence oxytocin secretion increases. In addition, the oxytocin cells discharge a burst of action potentials as each fetus passes through the birth canal. Each burst causes the secretion of a pulse of oxytocin, which sharply increases uterine tone; these bursts depend upon auto-stimulation by oxytocin released from the dendrites of the magnocellular neurons in the supraoptic and paraventricular nuclei. With the exception of the opioid mechanism that emerges to restrain oxytocin cell responsiveness, the behavior of oxytocin cells and their inputs in pregnancy and parturition is explicable from the effects of hormones of pregnancy (relaxin, estrogen, progesterone) on pre-existing mechanisms, leading through relative quiescence at term inter alia to net increase in oxytocin storage, and reduced auto-inhibition by nitric oxide generation. Cyto-architectonic changes in parturition, involving evident retraction of glial processes between oxytocin cells so they get closer together, are probably a response to oxytocin neuron activation rather than being essential for their patterns of firing in parturition.
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PMID:The magnocellular oxytocin system, the fount of maternity: adaptations in pregnancy. 1260 99

Orexin (hypocretin)-containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration of orexin peptides increases food intake, and orexin neurones in the LH are activated by hypoglycaemia during fasting. In addition, administration of orexins into the fourth ventricle or the dorsal motor nucleus of the vagus (DMV) has been shown to stimulate gastric acid secretion and motility, respectively, via vagal efferent pathways. In this study, whole-cell recordings were obtained from DMV neurones in rat brainstem slices to investigate the cellular mechanism(s) by which orexins produce their gastrostimulatory effects. To determine whether responsiveness to orexins might be differentially expressed among distinct populations of preganglionic vagal motor neurones, recordings were made from neurones whose projections to the gastrointestinal tract had been identified by retrograde labelling following apposition of the fluorescent tracer DiI to the gastric fundus, corpus or antrum/pylorus, the duodenum or caecum. Additionally, the responses of neurones to orexins were compared with those produced by oxytocin, which acts within the DMV to stimulate gastric acid secretion, but inhibits gastric motor function. Bath application of orexin-A or orexin-B (30-300 nM) produced a slow depolarization, accompanied by increased firing in 47 of 102 DMV neurones tested, including 70 % (30/43) of those that projected to the gastric fundus or corpus. In contrast, few DMV neurones that supplied the antrum/pylorus (3/13), duodenum (4/18) or caecum (1/13) were responsive to these peptides. The depolarizing responses were concentration dependent and persisted during synaptic isolation of neurones with TTX or Cd2+, indicating they resulted from activation of postsynaptic orexin receptors. They were also associated with a small increase in membrane resistance, and in voltage-clamp recordings orexin-A induced an inward current that reversed near the estimated equilibrium potential for K+, indicating the depolarization was due in large part to a reduction in K+ conductance. Orexins did not affect synaptically evoked excitation, but did reduce membrane excitability in a subset of gastric-projecting DMV neurones by enhancing GABA-mediated synaptic input. Lastly, although many DMV neurones responded to orexins and oxytocin with excitation, for the most part these peptides modulated excitability of distinct populations of gastric-projecting vagal motor neurones. These results indicate that orexins act preferentially within the DMV to directly excite vagal motor neurones that project to gastric fundus and corpus. In this way, release of endogenous orexins from descending hypothalamic projections into the DMV may mediate the increase in gastric acid secretion and motor activity associated with the cephalic phase of feeding.
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PMID:Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin. 1267 67

The mechanism by which dopamine induces or facilitates neurohypophysial hormone release is not completely understood. Because oxytocin- and vasopressin-secreting supraoptic neurons are under the control of a prominent GABAergic inhibition, we investigated the possibility that dopamine exerts its action by modulating GABA-mediated transmission. Whole cell voltage-clamp recordings of supraoptic neurons were carried out in acute hypothalamic slices to determine the action of dopamine on inhibitory postsynaptic currents. Application of dopamine caused a consistent and reversible reduction in the frequency, but not the amplitude, of miniature synaptic events, indicating that dopamine was acting presynaptically to reduce GABAergic transmission. The subtype of dopamine receptor involved in this response was characterized pharmacologically. Dopamine inhibitory action was greatly reduced by two highly selective D4 receptor antagonists L745,870 and L750,667 and to a lower extent by the antipsychotic drug clozapine but was unaffected by SCH 23390 and sulpiride, D1/D5 and D2/D3 receptor antagonists, respectively. In agreement with these results, the action of dopamine was mimicked by the potent D4 receptor agonist PD168077 but not by SKF81297 and bromocriptine, D1/D5 and D2/D3 receptor agonists, respectively. Dopamine and PD168077 also reduced the amplitude of evoked inhibitory postsynaptic currents, an effect that was accompanied by an increase in paired-pulse facilitation. These data clearly indicate that D4 receptors are located on GABA terminals in the supraoptic nucleus and that their activation reduces GABA release in the supraoptic nucleus. Therefore dopaminergic facilitation of neurohypophysial hormone release appears to result, at least in part, from disinhibition of magnocellular neurons caused by the depression of GABAergic transmission.
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PMID:Dopamine D4 receptor-mediated presynaptic inhibition of GABAergic transmission in the rat supraoptic nucleus. 1271 14

Corticolimbic circuits involving the prefrontal cortex, amygdala, and ventral striatum determine the reward value of food and might play a role in environmentally induced obesity. Chemical manipulation of the nucleus accumbens shell (AcbSh) has been shown to elicit robust feeding and Fos expression in the hypothalamus and other brain areas of satiated rats. To determine the neurochemical phenotype of hypothalamic neurons receiving input from the AcbSh, we carried out c-Fos/peptide double-labeling immunohistochemistry in various hypothalamic areas known to contain feeding peptides, from rats that exhibited a significant feeding response after AcbSh microinjection of the GABA(A) agonist muscimol. In the perifornical area, a significantly higher percentage of orexin neurons expressed Fos after muscimol compared with saline injection. In contrast, Fos expression was not induced in melanin-concentrating hormone and cocaine-amphetamine-related transcript (CART) neurons. In the arcuate nucleus, Fos activation was significantly lower in neurons coexpressing CART and proopiomelanocortin, and there was a tendency for higher Fos expression in neuropeptide Y neurons. In the paraventricular nucleus, no significant activation of oxytocin and CART neurons was found. Thus AcbSh manipulation may elicit food intake through coordinated stimulation of hypothalamic neurons expressing orexigenic peptides and suppression of neurons expressing anorexigenic peptides. However, activation of many neurons not expressing these peptides suggests that additional peptides/transmitters in the lateral hypothalamus and accumbens projections to other brain areas might also be involved.
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PMID:Peptides that regulate food intake: appetite-inducing accumbens manipulation activates hypothalamic orexin neurons and inhibits POMC neurons. 1273 70


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