Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurohypophysial hormone receptors were studied in myometrial specimens obtained from nonpregnant women using binding and in vitro contractility studies. The mathematical modeling of self- and cross-competition curves among [3H]oxytocin (OT), [3H]arginine vasopressin, the V1 vasopressin (VP) antagonist [3H]d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and the OT agonist [Thr4, Gly7] OT strongly indicates the presence of multiple classes of OT and arginine vasopressin receptors. The latter show the same pharmacological characteristics as the neurohypophysial hormone receptors described by our group for the human pregnant myometrium; in addition, they regulate the contractility of uterine strips. Blocking experiments were performed to evaluate the relative OT and V1 VP receptor distribution in 30 uterine specimens obtained from normal cycling and postmenopausal women. The glucuronoconjugate metabolites of 17 beta-estradiol and progesterone were also measured in 16 patients in early morning urine samples taken the same day as surgery. Our results show that V1 VP receptors are not only present but also biologically active in all the uterine specimens studied with virtually equal density in normal cycling and postmenopausal women. However, their concentrations do not correlate with either estrogen or progesterone urinary levels. The lowest OT receptor density was found at mid-cycle and in menopause, independently of any correlation with the urinary estrogens. Conversely, OT receptors rise sharply in the late luteal phase and during menstruation. In addition they show a positive relationship with glucuronoconjugate metabolites of progesterone levels. These results indicate that progesterone does not inhibit the expression of uterine OT receptors in the human uterus. Furthermore, they imply that neurohypophysial hormones are involved in the control of uterine activity during the menstrual cycle.
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PMID:Sex steroid modulation of neurohypophysial hormone receptors in human nonpregnant myometrium. 130 35

Magnocellular neurons synthesize vasopressin (VP) or oxytocin (OT) and release these hormones preferentially from the neural lobe during physiological stimulation. In the rat, VP is secreted preferentially during dehydration and hemorrhage, whereas OT is released without VP by suckling, parturition, stress, and nausea. Vasopressinergic neurons also synthesize and release dynorphin-related peptides--alpha- and beta-neoendorphin, dynorphin A (1-8) or (1-17), dynorphin B--which are agonists selective for kappa opiate receptors in the neural lobe. We proposed that one mechanism for preferential secretion of neurohypophysial hormones is that a dynorphin-related peptide(s) coreleased with VP inhibits selectively OT secretion from magnocellular neurons. We tested this hypothesis in conscious adult male Sprague-Dawley rats which were stimulated by either hypertonic saline administered intraperitoneally (2.5%, 20 ml/kg) or subcutaneously (1 M, 15 ml/kg) or by 24 h of water deprivation. Two approaches were used: (1) dynorphin-related peptides (0.02-20.4 mM) were injected intracerebroventricularly 1 min before decapitating the animal, and (2) the action of endogenous opioid peptides was blocked by injecting subcutaneously or intracerebroventricularly either naloxone or a selective kappa receptor antagonist, Mr 2266 or nor-binaltorphimine. VP and OT were measured by radioimmunoassay. After 24 h of water deprivation, the elevation in plasma [OT] but not [VP] was attenuated (p less than 0.05) by alpha-neoendorphin. Dynorphin A (1-8) also inhibited the release of OT and not VP after intraperitoneal administration of hypertonic saline. Blocking the action of endogenous opioid peptides at kappa receptors with Mr 2266 given peripherally (s.c.) elevated plasma [OT] but not [VP] after stimulation with hypertonic saline administered intraperitoneally or subcutaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kappa opiate receptors inhibit release of oxytocin from the magnocellular system during dehydration. 197 12

We have recently demonstrated the presence of two classes of neurohypophysial hormone receptors in the vagina, myometrium, and oviduct of rabbit: an oxytocin (OT) site and a V1 arginine vasopressin (AVP) site. We now report binding and in vitro contractility studies on human myometrial specimens obtained at cesarean section from women at the end of pregnancy. The program Ligand was used to analyze self- and cross-displacement curves for labeled OT, AVP or its V1 antagonist d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and selective analogs. Our results clearly indicate the presence of heterogeneity of binding sites in human uterus. Blocking experiments were performed to evaluate the density of OT and V1 AVP receptors in individual uterine specimens. The contractile response of the same samples to OT, AVP, and analogs was also evaluated. Our results indicate that V1 AVP receptors are present in all of the uterine specimens investigated, with virtually equal density from 32 weeks to term. AVP and the V1-selective agonist [Phe2,Ile3,Orn8]VP stimulate contractility of uterine strips, an effect blocked by nanomolar concentration of the V1 antagonist d(CH2)5TyrMeAVP. Uterine OT receptors increase during late pregnancy, peaking in early labor. A significant correlation between the density of OT receptors and the frequency of uterine contractions (external tocography) was found in pregnant women before surgery. OT stimulated in vitro contractility of uterine strips only when the density of receptors was more than 150 fmol/mg protein. In conclusion, we identified biologically active V1 AVP receptors in human uterus at the end of gestation and confirmed the primary relevance of OT receptors in human parturition.
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PMID:Human myometrium during pregnancy contains and responds to V1 vasopressin receptors as well as oxytocin receptors. 215 88

Opioids intrinsic to the neurohypophysis inhibit secretion from magnocellular neurosecretory terminals. This study examined whether the actions of opioids are mediated via interactions with neurohypophysial catecholamine systems. Blocking the action of intrinsic opioids in the isolated neurohypophysis with naloxone enhanced evoked secretion of oxytocin (OXT) by 150% and of vasopressin (AVP) by 30%. The enhancement of OXT secretion was not significantly altered in neurohypophyses depleted of greater than 90% of noradrenaline content by prior lesion of the ventral noradrenergic tract, or depleted of greater than 90% of both noradrenaline and dopamine content by prior reserpine treatment. Significant enhancement of AVP secretion by naloxone did not occur following depletion of catecholamines. The data suggest: (1) the majority of the influence of intrinsic opioids on secretion of OXT is not mediated via interaction with noradrenaline or dopamine systems, (2) the weaker influence of intrinsic opioids over AVP secretion may be mediated via catecholamines, (3) the majority of neurohypophysial noradrenaline is derived from projections of ascending medullary cell groups.
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PMID:Opioid inhibition of secretion from oxytocin and vasopressin nerve terminals following selective depletion of neurohypophysial catecholamines. 324 53

We have shown, using the opiate receptor antagonist naltrexone, that endogenous opioid peptides inhibit the release of oxytocin (OT), but not of vasopressin (AVP), from the hypothalamo-neurohypophysial system during dehydration. The stimulus for the release of neurohypophysial hormones during dehydration is both hypovolemia and increased plasma osmolality. The aims of this study were to determine whether opioid peptides inhibit OT secretion during an osmotic stimulus alone and, if so, to study the ontogeny of opiate inhibition of OT and AVP release during osmotic stimulation. Effects of endogenous opioid peptides were evaluated by injecting naloxone into immature and adult rats. Hypertonic saline was used as the osmotic stimulus. Adult male rats were injected sc with normal saline (0.85%; 1 ml/kg BW) or naloxone (5 mg/kg BW), followed 5 min later by normal or hypertonic (1 M) saline (15 ml/kg BW). After 170 min, a second injection of saline or naloxone was given; animals were decapitated 10 min later. Immature male and female rats at 2, 8, 21, and 30 days of age received 0.85% saline (1 ml/kg BW) or naloxone (5 mg/kg BW) ip 5 min before normal or hypertonic (2.5%) saline (20 ml/kg BW, ip). Pups were decapitated 15 min later. AVP and OT were measured by RIA in extracts of plasma, pituitaries, and hypothalami. In control rats, the contents of AVP and OT increased with age in both the pituitary and hypothalamus, attaining adult levels by day 21 for AVP and by day 30 for OT. In contrast, plasma concentrations of both AVP and OT were highest in 8-day-old rats and decreased thereafter to adult levels by 30 days of age. Hypertonic saline raised plasma osmolality 9-16 mosmol/kg H2O, increased AVP and OT concentrations in plasma of adults and immature rats at 2, 8, 21, and 30 days of age, and reduced pituitary stores of OT in adult animals. Blocking the action of opioid peptides with naloxone during osmotic stimulation augmented the rise in plasma OT in rats of all ages but further elevated plasma AVP only in immature rats. In adult animals, blocking opiate receptors with naloxone enhanced the depletion of OT stores from the pituitary, but did not affect the AVP content. We conclude that in the adult rat, endogenous opioid peptides inhibit OT release during osmotic stimulation, thereby allowing preferential release of AVP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ontogeny of opioid inhibition of vasopressin and oxytocin release in response to osmotic stimulation. 372 Jun 59

Naloxone, an opiate receptor antagonist, was used to determine whether opioid peptides modulate release of oxytocin (OT) or vasopressin (AVP) in the rat after expulsion of the fetus, i.e. parturition. We measured the concentrations of AVP and OT in plasma and in the neurointermediate lobe of the pituitary of pregnant rats given naloxone (5 mg/kg, s.c.) or saline on day 20 of gestation, and on day 21 either before or during the expulsive stage of labor. Non-pregnant rats in diestrus were given naloxone for comparison. On days 20 and 21 of gestation, before the onset of parturition, plasma [AVP] but not [OT] was elevated, compared to the non-pregnant controls. After delivery of the first two pups, plasma [OT] approximately doubled, whereas plasma [AVP] remained unchanged. Blocking the action of endogenous opioid peptides with naloxone caused an elevation of plasma [OT] in pregnant animals on days 20 and 21 of gestation and during parturition. Naloxone, however, did not alter plasma [AVP] in either parturient or preparturient animals. In contrast, [AVP], but not [OT], was increased in plasma of non-pregnant rats given naloxone. The content of OT in the neuro-intermediate lobe was similar in pregnant and non-pregnant rats and was unaffected by delivery of the first two pups. However, AVP content and the ratio of AVP/OT in the pituitary were lower in pregnant animals before and during delivery than in the non-pregnant controls. The content of neither hormone was altered by naloxone. Thus, AVP release apparently increases and pituitary stores of this peptide are decreased by day 20 of gestation, when labor has not yet begun.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of release of neurohypophysial hormones by endogenous opioid peptides in pregnant and parturient rats. 375 22

Central administration of an antagonist to the neuropeptide oxytocin (OT) has been shown to block the progesterone-induced facilitation of female sexual receptivity. In this study we examined the effects of infusing an OT antagonist (OTA) into various brain sites before rats were injected with 250 micrograms progesterone (P). Ovariectomized animals were injected daily for three consecutive days with 1 microgram estradiol benzoate and then on the fourth day were infused into the medial preoptic area (MPOA), medial basal hypothalamus (MBH) or ventral tegmental area with either 250 ng/microliter/side OTA or artificial cerebrospinal fluid vehicle. Animals were tested in an arena made of two white polyethylene cages connected by a tunnel that allowed passage of the female but not of the larger male. Several receptive and non-receptive behaviors were recorded for a 15-min period beginning 4 hr after P injection. Animals infused with OTA into the MPOA before P showed an increase in the frequency and total duration of fighting with males and the frequency of audible vocalizations made by females. OTA infusions also increased the frequency of mounts that did not result in a lordosis posture. OTA infusions into the MPOA also reduced the frequency and total duration of lordosis postures in response to mounts. OTA infusions into the MBH and VTA had no effect on measures of sexual behaviors. Blocking OT transmission in the MPOA resulted in increased rejection behaviors and decreased receptivity in females when infused before systemic P injection.
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PMID:Infusion of an oxytocin antagonist into the medial preoptic area prior to progesterone inhibits sexual receptivity and increases rejection in female rats. 781 8

The role of oxytocin (OT) in the regulation of prostaglandin F2 alpha (PGF2 alpha) secretion during luteolysis in gilts was studied using a highly specific OT antagonist (CAP-581). In Experiment 1 gilts on Days 14 to 19 of the oestrous cycle in Latin square design were used, to determine the dose and time of application of OT and CAP. In Group I (n = 6) gilts were treated intravenously with saline or with 10, 20 and 30 IU of OT. Concentrations of the main PGF2 alpha metabolite i.e. 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured in blood samples as uterine response to the treatment. Twenty IU of OT was the most effective to stimulate PGFM release and this dose was used after CAP treatment in gilts of Groups II, III and IV. Gilts of Group II (n = 3) were injected into the uterine horns (UH) with saline (5 ml/horn) or CAP (2 mg, 3 mg and 4 mg; half dose/horn) and OT was injected (i.v.) 30 min thereafter. Any of the CAP doses given into the UH affected PGFM plasma concentrations stimulated by OT. In Group III (n = 4) gilts were infused (i.v.) for 30 min with CAP (9 mg, 14 mg and 18 mg/gilt) followed by 20 IU of OT. All doses of CAP effectively inhibited OT-stimulated PGF2 alpha release, therefore 9 mg was selected for the further studies. Gilts of Group IV (n = 4) received OT 4, 6 and 8 h after CAP to define how long CAP blocks the OT receptors. Concentrations of PGFM increased after any of this period of time. Thus, we concluded that 9 mg of CAP infused every 4 h will effectively block OT receptors. In Experiment 2, gilts (n = 4) received CAP as a 30-min infusion every 4 h on Days 12-20 of the oestrous cycle. Control gilts (n = 3) were infused with saline. CAP infusions diminished the height of PGFM peaks (P < 0.05). Frequency of the PGFM (P < 0.057) and OT (P < 0.082) peaks only tended to be lower in the CAP-treated gilts. Peripheral plasma concentrations of progesterone (P4) and oestradiol-17 beta (E2) and the time of luteolysis initiation as measured by the decrease of P4 concentration were the same in CAP- and saline-treated gilts. The macroscopic studies of the ovaries in gilts revealed lack of differences between groups. We conclude that OT is involved in the secretion of luteolytic PGF2 alpha peaks but its role is limited to controlling their height and frequency. Blocking of OT receptors did not prevent luteolysis in sows.
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PMID:Effect of an oxytocin antagonist on prostaglandin F2 alpha secretion and the course of luteolysis in sows. 1034 85

The aim of this study was to investigate effects of oxytocin (OT) on electrical neuronal activities in rat subfornical organ (SFO) and compare its action with the well-described excitatory effects of blood-borne angiotensin II (ANG II) on the same SFO neurons. With the use of extracellular recordings from spontaneously active neurons in slice preparations of the SFO of male rats, 11.7% of tested neurons (n = 206) were excited and 9.7% were inhibited by superfusion with 10(-6) M OT. Both excitatory and inhibitory effects of OT were dose dependent with similar threshold concentrations and were blocked by a specific OT-receptor antagonist but not by a vasopressin receptor antagonist. Blocking synaptic transmission with low calcium medium suppressed only inhibitory effects of OT. All but one of the OT-sensitive neurons were also excited by superfusion with ANG II at a concentration much lower than required for OT, suggesting that synaptically released OT rather than blood-borne OT alters the activity of SFO neurons in vivo. The results support the hypothesis that neurally released OT may modulate SFO-mediated functions by acting on OT-sensitive neurons.
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PMID:Neuronal actions of oxytocin on the subfornical organ of male rats. 1036 11

We studied the effects of the neuropeptide oxytocin (OT) on the long-term potentiation (LTP) paradigm in the dentate gyrus (DG) of urethane anesthetized rats. Intracerebroventricular injection of 1 microg of the hormone in 1 microl of physiological solution 2min before tetanization produced a significant decrease in both components of the perforant path evoked potentials (EP) in the DG. The effects appeared right after the tetanization stimuli and were more pronounced in the excitatory postsynaptic components of the EPs. The decrements lasted for the 2h of recording time. We concluded that OT induced and maintained long-term depression on the DG. In contrast, injection of OT in the absence of tetanic stimulation did not significantly affect perforant path EP in the DG. The results are discussed taking particular consideration of the inhibitory effects the OT has on (Ca(2+)+Mg(2+)) ATPase at membrane levels and the potential interference that this action may have with phosphorylation processes via an ectoprotein kinase isolated from membranes of hippocampal pyramidal neurons. Blocking of this ectoprotein kinase in vitro significantly impairs establishment and maintenance of LTP.
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PMID:Oxytocin induces long-term depression on the rat dentate gyrus: possible ATPase and ectoprotein kinase mediation. 1212 11


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