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

The actions of opioids on electrically evoked release of oxytocin, vasopressin, and noradrenaline-using the [3H]-noradrenaline technique-from the rat neurohypophysis were examined in vitro. Antagonism of the action of endogenous neurohypophysial opioids with naloxone enhanced release of peptides and [3H]-noradrenaline differentially. Naloxone enhanced oxytocin release by 100 and 173% in two series of experiments (ED50 7 x 10(-7) M), whilst vasopressin release was enhanced by only 30 and 20%, respectively. [3H]-noradrenaline release was maximally enhanced by 41% (ED50 2 x 10(-7) M). We examined the opioid receptor subtypes mediating these effects using selective receptor agonists. The kappa-agonist U-50,488H inhibited oxytocin and vasopressin release to a similar extent, but did not modify [3H]-noradrenaline release. The effects of U-50,488H were completely prevented by a tenfold molar excess of naloxone. The mu-agonist (D-Ala2, MePhe5 Gly-ol)-enkephalin also failed to inhibit [3H]-noradrenaline release and caused only a minor inhibition of oxytocin and vasopressin secretion. The delta-agonist (D-Pen2, D-Pen5)-enkephalin was without effect. We conclude that (1) kappa-receptors sensitive to U-50,488H mediate opioid inhibition of secretion from oxytocin and vasopressin nerve terminals; (2) when opioid actions are blocked by naloxone, opioid peptides within the neurohypophysis are shown to exert a much greater influence over oxytocin compared to vasopressin terminals; (3) neurohypophysial opioids also regulate release from noradrenergic terminals, although the nature of the receptors involved remains unclear, and (4) kappa-receptors can mediate inhibition of neurohormone secretion by an action independent of the neurohypophysial noradrenergic innervation.
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PMID:Opioid-noradrenergic interactions in the neurohypophysis. I. Differential opioid receptor regulation of oxytocin, vasopressin, and noradrenaline release. 284 91

The rat neurohypophysis contains both opioid receptors and substantial amounts of endogenous opioid peptides. Inhibitory influences of opioids on the secretion of both oxytocin and vasopressin have been described. We have examined the effects of a range of opioid agonists and antagonists with differing relative selectivities towards opioid receptor subclasses on the secretion of oxytocin and vasopressin from the isolated neurohypophysis. Oxytocin and vasopressin release evoked by brief periods of electrical stimulation in control experiments was compared to evoked release in the presence of test compounds. Oxytocin release was depressed approximately 25% by the delta-agonist (D-Ala2, D-Leu5)-enkephalin but not affected by putative kappa-agonists or by beta-endorphin. The use of opioid antagonists revealed a strong inhibition of oxytocin secretion by endogenous opioids released during electrical stimulation. Naloxone, relatively mu-selective, enhanced oxytocin secretion by up to 90% with a half-maximal effect at approximately 10(-6) M. MR2266, a relatively kappa-selective antagonist also enhanced oxytocin secretion but displayed agonist-like activity at high concentrations. ICI 154129, a delta-selective antagonist, was without effect on oxytocin secretion. Vasopressin release was unaffected by any of the agonists tested and not potentiated by antagonists at a range of stimulation frequencies. The data do not support the suggestion of an inhibitory endogenous opioid influence over vasopressin secretion within the neurohypophysis but indicate that an endogenous opioid peptide, possibly acting via mu- or kappa rather than delta-receptors, strongly suppresses the secretion of oxytocin.
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PMID:Effects of opioid agonists and antagonists on oxytocin and vasopressin release in vitro. 286 49

Oxytocin release from the rat neurohypophysis is under endogenous opioid inhibition. It has recently been established that dynorphin precursor-derived peptides are colocalized with vasopressin (VP) in the secretory granules in nerve terminals of the neural lobe, and that the opiate receptors in the neural lobe are restricted to the kappa-subtype. Therefore, we hypothesized that dynorphin, which is copackaged and thus coreleased with VP, is the endogenous opioid that inhibits release from neighboring oxytocin (OT) terminals. To test this hypothesis we examined the effects of dynorphin-(1-8), dynorphin-(1-17), and naloxone on the electrically stimulated release of OT and VP from isolated rat neurointermediate lobes throughout a range of stimulus frequencies. Both dynorphin-(1-8) and -(1-17) (2 microM) produced a substantial reduction in OT release during a 4-Hz stimulus, and this effect was abolished by naloxone (10 microM). Neither form of dynorphin, however, affected OT secretion at a stimulus frequency of 12 or 30 Hz at concentrations up to 10 microM. Naloxone (10 microM) by itself did not affect OT release during the 4-Hz stimulus, but it produced a substantial increase in OT release at a stimulus frequency of 12 Hz. In contrast, neither form of dynorphin produced inhibition, nor did naloxone augment VP secretion at any frequency tested. Frequency-dependent secretion curves (4, 8, 12, 20, and 30 Hz) for OT and VP in the presence and absence of naloxone indicated that the degree of naloxone augmentation of OT release at a given stimulus frequency was positively correlated with the amount of VP release at that frequency. These data support the hypothesis that dynorphin released in parallel with VP during in vitro stimulations of the rat neurohypophysis simultaneously inhibits stimulated OT release.
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PMID:Dynorphin A inhibits and naloxone increases the electrically stimulated release of oxytocin but not vasopressin from the terminals of the neural lobe. 289 96

1. Lactating rats were implanted with a cannula in a lateral cerebral ventricle to deliver morphine (up to 50 micrograms/h) chronically from a subcutaneous osmotically driven mini-pump. After infusion of morphine for 5 days the rats were anaesthetized with urethane and prepared with ventral surgery for recording the electrical activity of single, antidromically identified neurones in the supraoptic nucleus. 2. A single I.V. injection of naloxone (5 mg/kg) in these rats provoked a long-lasting, large increase in intramammary pressure, but in control rats had negligible effects. Concentrations in plasma of oxytocin, measured by radioimmunoassay in samples of femoral arterial blood, rose from 44.7 +/- 2.5 to 1072.1 +/- 89.5 pg/ml (means +/- S.E.M.) 6 min after naloxone in the morphine-treated rats. In control rats, the concentration of oxytocin in plasma rose only from 42.1 +/- 2.9 to 125.1 +/- 28.2 pg/ml after naloxone. 3. Naloxone produced a transient increase in arterial blood pressure in morphine-treated but not control rats. Concentrations in plasma of vasopressin, measured by radioimmunoassay in samples of femoral arterial blood, rose in morphine-treated rats from 7.4 +/- 2.4 to 29.2 +/- 3.7 pg/ml after naloxone, but did not rise significantly in control rats. 4. Naloxone (1-5 mg/kg) produced a prompt and prolonged increase in the discharge rate of each of ten continuously active (putative oxytocin) cells recorded from ten morphine-treated rats. The discharge rate of the six cells tested at the highest dose (5 mg/kg) increased by an average of 6.3 Hz (360%) within 5 min, and the firing rate remained elevated for at least 30 min; the discharge rate of six continuously active supraoptic neurones recorded in control rats was not affected by naloxone. 5. The firing activity of five phasic (putative vasopressin) supraoptic neurones in morphine-treated rats was increased for at least 30 min by the injection of naloxone; these increases were the result of a raised intraburst firing rate with no change in burst duration or frequency. One phasic neurone was inhibited for 15 min, and one phasic neurone was unaffected. 6. The excitatory effects of naloxone on neurones in the supraoptic nucleus of morphine-treated rats were not explained by changes in blood pressure or osmolarity and did not depend on suckling or a cholinergic pathway. 7. The concentrations of oxytocin in plasma and the operation of the milk-ejection reflex were similar in the controls and morphine-treated rats, prior to naloxone. These findings indicate tolerance to initial inhibitory effects of morphine on oxytocin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment. 290 Aug 90

Blood was collected from freely moving rabbits pretreated with saline or naloxone both before and after coitus. In the males, ejaculation was associated with a marked increase in plasma oxytocin concentrations. In the females, oxytocin release was an all-or-nothing phenomenon-either there was no change in oxytocin or it rose to levels very similar to that found post-ejaculation in the males. Naloxone did not alter the proportion of occasions in which females showed an oxytocin response, nor did it have a significant effect on the levels of oxytocin achieved during coitus in either the male or the female rabbits.
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PMID:Oxytocin release during coitus in male and female rabbits: effect of opiate receptor blockade with naloxone. 302 95

Stress induced oxytocin (OT) secretion was measured in female rats following treatment with various opiate antagonists selective for different types of opiate receptor. Naloxone (mu selective) and MR2266 BS (kappa selective) potentiated the OT response to an emotional stress (1 min. immobilization) whereas the delta selective antagonist ICI 154129 was without effect. Similarly, naloxone and MR2266 BS, but not ICI 154129, potentiated the response to a physical stress (i.p. hypertonic saline). A dose response comparison of the actions of naloxone and MR2266 BS revealed that naloxone was most effective in potentiating the immobilization response whereas MR2266 BS elicited greater responses than naloxone when administered prior to hypertonic saline. The results indicate that the opioid regulation of stress induced OT secretion is primarily mediated via mu and kappa opiate receptor types, the two types differentially regulating the OT response to two different stressors.
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PMID:Opioid control of oxytocin secretion: evidence of distinct regulatory actions of two opiate receptor types. 303 9

Blood samples were taken from conscious, chronically-catheterized rats during parturition for measurement of oxytocin by specific radioimmunoassay. After the birth of the 3rd pup, rats were allowed to remain in their nesting cage (undisturbed rats) or were transferred for 45 min to a glass bowl (disturbed rats); at the time of transfer, rats were given an i.v. injection of the opioid antagonist naloxone or saline vehicle. Subsequent parturition was prolonged in saline-treated disturbed rats, but not in naloxone-treated disturbed rats. Parturition was significantly hastened in naloxone-treated undisturbed rats. Naloxone injections were followed by a large rise in plasma oxytocin concentrations in disturbed and undisturbed rats. We conclude, from a statistical analysis of the relationship within experimental groups between plasma oxytocin concentration and speed of parturition, that the effects of disturbance and of naloxone upon parturition may be accounted for, at least in part, by their effects upon oxytocin release. However, the effects of disturbance on parturition may not be mediated entirely by activation of opioid pathways. Naloxone did not potentiate oxytocin release in non-pregnant rats, or on Day 1 post partum, but did potentiate oxytocin release on Day 22 of pregnancy even in rats before the onset of parturition. Endogenous opioid pathways regulating oxytocin release therefore appear to be active during late pregnancy and during parturition itself.
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PMID:Endogenous opioid actions and effects of environmental disturbance on parturition and oxytocin secretion in rats. 318 53

The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.
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PMID:Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man. 321 43

1. Rats underwent either: (1) acute or chronic morphine or naloxone administration; (2) simple morphine withdrawal or naloxone-precipitated withdrawal in morphine-dependent animals; or (3) stress from I.P. administration of hypertonic saline. 2. Quantitative in situ hybridization histochemistry was performed using synthetic oligonucleotide probes for corticotrophin-releasing factor (CRF), vasopressin, pro-opiomelanocortin (POMC), dynorphin, enkephalin and oxytocin mRNAs. The paraventricular and supraoptic nuclei were examined in all studies and the arcuate nucleus and pituitary gland in the acute withdrawal study. 3. Neither acute nor chronic morphine administration altered either (a) hypothalamic parvocellular or magnocellular CRF mRNA, or (b) anterior pituitary or pars intermedia POMC mRNA. 4. Naloxone-precipitated morphine withdrawal resulted in a marked increase in parvocellular (but not magnocellular) CRF mRNA within 4 h and levels remained elevated through 24 h. There was no change in arcuate nucleus or pars intermedia POMC mRNA, but in the anterior pituitary there was a delayed increase, significant at 24 h. 5. Simple morphine withdrawal without the use of naloxone did not result in any change in CRF mRNA but there were increases in magnocellular vasopressin and dynorphin mRNA, presumably related to decreased water intake. 6. Intraperitoneal hypertonic saline stress also resulted in a marked accumulation of both parvocellular CRF and vasopressin mRNA without any concomitant change in magnocellular vasopressin mRNA. Increased translation of CRF mRNA was also evidenced by increased immunoreactive CRF detected by immunocytochemistry.
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PMID:Corticotrophin-releasing factor, vasopressin and pro-opiomelanocortin mRNA responses to stress and opiates in the rat. 326 21

We have investigated the secretion of oxytocin and arginine vasopressin (AVP) during vaginocervical stimulation in the conscious goat and examined the effect of the opioid antagonist naloxone on peptide release to this stimulus. Goats were implanted with guide tubes overlying the cisterna magna under anaesthesia and allowed to recover. Vaginocervical stimulation for 60 s resulted in a marked (P less than 0.01) release of oxytocin into the plasma but neither plasma AVP nor cerebrospinal fluid (CSF) concentrations of oxytocin changed significantly. In a second series of experiments, unoperated goats were infused with saline or naloxone (4 mg bolus + 12 mg/h) in random order on two separate occasions. Infusion of naloxone had no effect on basal plasma concentrations of oxytocin or AVP. There was a marked and significant (P less than 0.01) potentiation of oxytocin secretion following vaginocervical stimulation in animals infused with naloxone. Naloxone-infused animals showed a significant (P less than 0.01) rise in plasma AVP after stimulation but plasma AVP did not change in the saline-infused controls. We conclude that vaginocervical stimulation leads to the selective release of oxytocin from the neurohypophysis without affecting concentrations of oxytocin in the CSF. Endogenous opioids inhibit the stimulated secretion of oxytocin and AVP in vivo in response to vaginocervical stimulation in the goat.
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PMID:Effect of naloxone on oxytocin and vasopressin release during vaginocervical stimulation in the goat. 343 51


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