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

Endogenous opioid regulation of neurohypophysial and hypothalamo-pituitary-adrenal (HPA) axis hormone secretion in response to forced swimming (90 s in deep water at 19 degrees C) was investigated in virgin and 21-day-pregnant rats. There was no difference in basal plasma oxytocin concentrations between pregnant and virgin rats, but the opioid antagonist, naloxone, increased basal oxytocin secretion in the pregnant rats. Forced swimming increased oxytocin secretion similarly in pregnant and virgin rats, and this response was enhanced by naloxone. In pregnant rats naloxone had a greater effect (by 3.1-fold) than in virgins, showing stronger endogenous opioid restraint of an enhanced oxytocin secretory response to stress in pregnancy. Vasopressin secretion was not increased with forced swimming in virgin or pregnant rats, and naloxone had no effect. ACTH and corticosterone secretion in response to forced swimming was attenuated in pregnant rats compared to virgin rats, measured at 5 min. Naloxone had no effect on basal plasma ACTH or corticosterone concentration, but it reduced ACTH secretion in virgin rats 5 min after forced swimming; in pregnant rats naloxone had no such effect. Naloxone removed the pregnancy-related attenuation in corticosterone secretion measured at 5 min after forced swimming. Fifteen minutes after forced swimming, plasma corticosterone concentrations were not different between groups. In the late-pregnant rats, the increases in plasma ACTH and corticosterone induced by forced swimming were significantly prolonged compared to virgins. The results show that endogenous opioid inhibition emerges in pregnancy to restrict the responses of oxytocin neurones to a stressor. In contrast, the endogenous opioid enhancement of mechanisms regulating HPA axis secretory responses in virgin rats is not evident during pregnancy.
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PMID:The role of endogenous opioids in neurohypophysial and hypothalamo-pituitary-adrenal axis hormone secretory responses to stress in pregnant rats. 977 73

The aim of this study was to investigate the action of opioids (the mu receptor agonist morphine) and the antagonist naloxone on inhibition of oxytocin release and milk let-down in response to milking in dairy cows. In the first experiment, cows were injected with 0, 21, 70 and 210 mg morphine 10 min before milking on four successive days. Plasma oxytocin levels after 1 min manual stimulation of the udder were reduced by 70 and 210 mg morphine, and milk let-down was inhibited at the latter dose. In the second experiment, cows were injected after a control milking with 210 mg morphine (or 350 mg at 10 min before milking the following day if not effective) to inhibit milk flow. On the following day the inhibiting dose of morphine was given with 210 mg naloxone. Naloxone injection given before morphine had no effect on plasma oxytocin concentrations, but abolished the inhibition of oxytocin release by morphine and potentiated oxytocin release in response to milking. Naloxone alone injected the day after control milking increased oxytocin levels during milking, suggesting involvement of the opioid system in milking. A model has been developed for the control of opioid effects during milking. Morphine suppressed oxytocin release during milking in a dose-dependent manner and the effect was reversible by naloxone.
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PMID:Effects of morphine and naloxone on the release oxytocin and on milk ejection in dairy cows. 1071 39

In pregnancy, endogenous opioids inhibit enhanced basal and stressor-stimulated oxytocin neurone activity and secretion. By contrast, stress responses of the hypothalamo-pituitary-adrenal (HPA) axis are reduced in pregnancy. We investigated whether the high levels of oestradiol and progesterone of pregnancy could induce these changes. Silastic capsules containing oestradiol or progesterone (or control capsules) were implanted s.c. in virgin female rats for 16 or 17 days, with or without progesterone removal on day 15 to mimic the progesterone withdrawal seen at the end of pregnancy. Plasma concentrations of oxytocin, adrenocorticotrophic hormone (ACTH) and corticosterone were measured in jugular vein blood samples from conscious rats. Under basal conditions, naloxone (5 mg/kg) increased oxytocin secretion in all groups, but had no greater effect in sex-steroid treated rats, and did not induce Fos expression in the supraoptic nucleus. Forced swimming, a stressor, increased oxytocin secretion at 5 min in vehicle-injected controls, and this response was slightly attenuated in the sex-steroid treated groups. Pretreatment with naloxone greatly enhanced the response in the sex-steroid treated rats, and was less effective in the controls. In rats treated with oestradiol alone, naloxone prolonged the response. Thus, the combined sex-steroid treatment enhanced the responsiveness of oxytocin neurones to the stressor, while simultaneously restraining oxytocin secretion via endogenous opioid inhibition. In the same rats, ACTH and corticosterone secretion was also stimulated by the stressor, but the hypothalamo-pituitary-adrenal (HPA) axis response was not attenuated in sex-steroid treated rats. Naloxone weakly reduced the HPA axis response in controls and was ineffective in the sex-steroid treated rats. We conclude that oestradiol and progesterone may be responsible for inducing the opioid restraint and enhanced oxytocin neurone responsiveness in pregnancy.
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PMID:Sex-steroid induction of endogenous opioid inhibition on oxytocin secretory responses to stress. 1071 31

This experiment tested the hypothesis that opioid antagonists could influence the timing of the onset and progress of parturition in the pig. Primiparous pigs (gilts) received a jugular catheter on Days 104 to 106 of pregnancy. At 1400 h on Day 112 the gilts received 10 mg PGF2alpha, i.m. to induce parturition. At 1000 h on Day 113 (i.e., 20 h later) gilts received either saline (n=6), 1 mg/kg, i.v. naltrexone (n=4) or 1 mg/kg, i.v. naloxone (n=5). Blood samples were taken daily from Days 108 to 116. On Day 113, blood samples were taken hourly from 0500 to 0900 h and then every 30 min until 2400 h, or until the birth of the last piglet (BLP) (whichever was sooner) and assayed for progesterone, oxytocin (OT), cortisol and PRL. Additional blood samples for OT and cortisol assay were taken every minute from 0930 to 1100 h on Day 113 and for 30 min during parturition. Naloxone, but not naltrexone, delayed the onset of parturition relative to saline controls (by 14 h 21 min; P<0.05). Duration of parturition and rate of births were not significantly affected by treatment. Mean plasma OT increased in the 4 h following naloxone but not saline treatment, during which time OT plasma pulse amplitude was reduced in naloxone and naltrexone-treated animals relative to saline treated controls. The PRL secretion rose following treatment in saline treated animals, consistent with approaching parturition, but failed to rise in opioid antagonist treated animals. Progesterone concentrations remained elevated in naloxone-treated animals for longer than in the other groups. These data suggest that a rapid change in overall effect of parenteral administration of naloxone to parturient pigs occurs from delaying its onset when administered as in these experiments, to facilitating its progress when given during parturition (earlier experiments). The delay of onset of parturition may be mediated by interference with hypothalamic control of OT or PRL release.
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PMID:The timing of parturition in the pig is altered by intravenous naloxone. 1073 Sep 79

Effect of chronic morphine treatment on oxytocin (OT) release from the long term-cultured organotypic slice of the supraoptic nucleus (SON) was investigated using radioimmunoassay. The co-localization of oxytocin and mu-opioid receptor in neurons within the SON was observed with the double-labeled methods of in situ hybridization combined with immunohistochemistry. After exposure to morphine for 6days, the OT levels in culture media were significantly decreased. Naloxone caused much greater release of OT in chronic morphine treatment group than in controls. Naloxone has no effect after acute morphine treatment. 90% of OT-ir (immunoreactive) neurons expressed mu-opioid receptor mRNA in the SON and 45% of the neurons that expressed mu-opioid receptor mRNAs were OT-ir neurons. These results indicated that the neurons within SON could develop dependence on morphine in vitro, and these effects might be exerted via mu-opioid receptor in oxytocin neurons of the SON.
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PMID:Chronic morphine treatment inhibits oxytocin release from the supraoptic nucleus slices of rats. 1117 38

To determine whether intrinsic mechanisms drive supraoptic nucleus oxytocin neuron excitation during morphine withdrawal, we calculated the probability of action potential (spike) firing with time after each spike for oxytocin neurons in morphine-naive and morphine-dependent rats in vivo and measured changes in intrinsic membrane properties in vitro. The opioid receptor antagonist, naloxone, increased oxytocin neuron post-spike excitability in morphine-dependent rats; this increase was greater for short interspike intervals (<0.1 s). Naloxone had similar, but smaller (P=0.04), effects in oxytocin neurons in morphine-naive rats. The increased post-spike excitability for short interspike intervals was specific to naloxone, because osmotic stimulation increased excitability without potentiating excitability at short interspike intervals. By contrast to oxytocin neurons, neither morphine dependence nor morphine withdrawal increased post-spike excitability in neighbouring vasopressin neurons. To determine whether increased post-spike excitability in oxytocin neurons during morphine withdrawal reflected altered intrinsic membrane properties, we measured the in vitro effects of naloxone on transient outward rectification (TOR) and after-hyperpolarization (AHP), properties mediated by K+ channels and that affect supraoptic nucleus neuron post-spike excitability. Naloxone reduced the TOR and AHP (by 20% and 60%, respectively) in supraoptic nucleus neurons from morphine-dependent, but not morphine-naive, rats. In vivo, spike frequency adaptation (caused by activity-dependent AHP activation) was reduced by naloxone (from 27% to 3%) in vasopressin neurons in morphine-dependent, but not morphine-naive, rats. Thus, multiple K+ channel inhibition increases post-spike excitability for short interspike intervals, contributing to the increased firing of oxytocin neurons during morphine withdrawal.
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PMID:Morphine withdrawal increases intrinsic excitability of oxytocin neurons in morphine-dependent rats. 1567 49

In recent years, oxytocin has been implicated in a wide diversity of functions. The role of oxytocin in analgesia and pain modulation represents an important new function of an endogenous system controlling sensorial information. The paraventricular (PV) nucleus of the hypothalamus is one of the most important sources of oxytocin, and it has a very well-defined projection to the spinal cord. The location of this PV spinal cord projection correlates well with oxytocin binding sites at the dorsal horn of the spinal cord. In this work, we used rats with a chronic (46 days) sciatic loose ligature, an electrical stimulating electrode, and an intrathecal cannula, which reached the L4-L5 levels of the spinal cord. We compared the oxytocin effects with electrical stimulation of the PV and observed a significant reduction of the withdrawal responses to mechanical and cold stimulation applied to the ipsilateral and contralateral hind paws. An oxytocin antagonist administered intrathecally blocked the PV effects. Naloxone was also intrathecally injected 2 min before the PV stimulation, and we also observed a significant reduction of the withdrawal responses; however, this reduction was less pronounced. Our results support the hypothesis that oxytocin is part of the descending inhibitory control mechanisms having an important antinociceptive action. We cannot exclude a minor opiate participation in the OT action.
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PMID:Oxytocin and electrical stimulation of the paraventricular hypothalamic nucleus produce antinociceptive effects that are reversed by an oxytocin antagonist. 1652

Cytokine challenge (mimicking infection) with systemic interleukin-1beta (IL-1beta) stimulates oxytocin neurons via a noradrenergic brainstem pathway similar to that involved in parturition. As the responses of oxytocin neurons to several stimuli are reduced in late pregnancy, we have investigated whether responses to IL-1beta are also suppressed. In virgin Sprague-Dawley rats, IL-1beta (500 ng/kg i.v.) rapidly increased oxytocin secretion (3.2-fold), via a central action as the firing rate of oxytocin neurons in the supraoptic nucleus was increased. In contrast, IL-1beta had no significant effect on the electrical or secretory activity of oxytocin neurons in late pregnant rats. In pregnancy activation of a central inhibitory opioid mechanism restrains oxytocin neuron responses to various stimuli. Accordingly, we tested the effects of the opioid antagonist, naloxone, on oxytocin neuron responses to IL-1beta in pregnancy. Naloxone (5 mg/kg i.v.) did not affect the oxytocin secretory response to IL-1beta in virgin rats, whereas in late pregnant rats naloxone revealed a greater oxytocin secretory response to IL-1beta (3.5-fold) than in virgin rats. In virgin rats, naloxone decreased oxytocin neuron firing rate after IL-1beta, however, in pregnant rats naloxone increased the firing rate response to IL-1beta to the level seen in virgin rats. Thus, systemic IL-1beta acts centrally to increase oxytocin secretion. In pregnancy this response is suppressed by endogenous opioids, thus preserving neurohypophysial oxytocin stores for parturition and minimizing the risk of preterm labour. The exaggerated oxytocin secretory response to IL-1beta in pregnancy after naloxone reflects increased oxytocin stores and/or increased efficiency of excitation-secretion coupling at the posterior pituitary.
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PMID:Suppressed oxytocin neuron responses to immune challenge in late pregnant rats: a role for endogenous opioids. 1655 86

During pregnancy, emergence of endogenous opioid inhibition of oxytocin neurons is revealed by increased oxytocin secretion after administration of the opioid receptor antagonist, naloxone. Here we show that prolonged estradiol-17beta and progesterone treatment (mimicking pregnancy levels) potentiates naloxone-induced oxytocin secretion in urethane-anesthetized virgin female rats. We further show that estradiol-17beta alone rapidly modifies opioid interactions with oxytocin neurons, by recording their firing rate in anesthetized rats sensitized to naloxone by morphine dependence. Naloxone-induced morphine withdrawal strongly increased the firing rate of oxytocin neurons in morphine dependent rats. Estradiol-17beta did not alter basal oxytocin neuron firing rate over 30 min, but amplified naloxone-induced increases in firing rate. Firing pattern analysis indicated that acute estradiol-17beta increased oxytocin secretion in dependent rats by increasing action potential clustering without an overall increase in firing rate. Hence, rapid estradiol-17beta actions might underpin enhanced oxytocin neuron responses to naloxone in pregnancy.
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PMID:Rapid estradiol-17beta modulation of opioid actions on the electrical and secretory activity of rat oxytocin neurons in vivo. 1796 Apr 80

Abstract We tested the hypothesis of a cross-inhibition of oxytocin (OT) release by endogenous opioid peptides co-released with vasopressin (VP). This opioid cross-inhibition resulted in a selective block of OT release and hence in preferential release of VP. The effects of the opiate receptor antagonist naloxone were tested on neurohypophyseal VP release during dehydration, ethanol administration and sulphated cholecystokinin octapeptide (CCK-8S) application, assuming that the inhibition of pituitary OT release by endogenous opioids increases as neurohypophyseal VP output increases. A high VP output was found to coincide with increased inhibition of OT release: Subcutaneous injection of graded doses of naloxone (30 min prior to decapitation), augmented OT plasma levels significantly more in 24 h water-deprived male rats than in normally hydrated rats. Naloxone had no effect on VP release. Ethanol (10% in saline) administered intragastrically 50 min prior to decapitation and 20 min before subcutaneous naloxone (5 mg/kg) resulted in the inhibition of VP output. The ethanol treatment resulted in a rise in plasma OT levels that was additional to the effect of naloxone. These features were present in normally hydrated as well as in 24 h water-deprived animals, but were more pronounced in the latter group. Peripheral CCK-8S administration induces an abrupt and selective secretion of OT. Blocking the opioid inhibition of OT release with naloxone resulted in a significant rise of OT compared to that with CCK-8S alone. The magnitude of the opioid inhibition coincided with the activity of the VP system, and a higher dose of naloxone was needed to potentiate the CCK-8S effect on OT release in the water-deprived group than in euhydrated rats. No effect of CCK-8S and/or naloxone was found on VP plasma levels. The data indicate that opioid peptides co-released with VP (like dynorphin) may be responsible for cross-inhibition of OT release during dehydration. This suggests that dynorphin acts in a paracrine way, making it a strong candidate for this role.
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PMID:Enhanced Neurohypophyseal Vasopressin Release is Associated with Increased Opioid Inhibition of Oxytocin Release. 1921 47


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