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

Oxytocin was iodinated using the thallium chloride method. Purification of iodination reaction mixture on Sephadex G-10 and G-15 was compared. Sephadex G-10 effected the separation of iodo-oxytocin from excess free radioiodide. Sephadex G-15 succeeded in separating iodinated from non-iodinated oxytocin as well as from readioiodide. It was found that the storage of unfractionated iodination mixture resulted in an apparent increase in the molecular size of iodinated hormone and that this process was accelerated at temperatures of -20 degrees in comparison with 4 degrees.
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PMID:Iodination and purification of oxytocin. 124 74

The birth of a flaccid neonate is described. Oxytocin, diazepam and extradural bupivacaine were used during labour. The baby survived 1 1/2 hours of artificial ventilation and was subsequently healthy. An account is given of the assessment of foetal maturity and the diagnosis of neonatal flaccidity is discussed.
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PMID:Neonatal flaccidity. Survival after neonatal respiratory failure with extreme flaccidity. 127 1

Oxytocin content has been measured by radioimmunoassay in microdissected hypothalamic nuclei. Equal concentrations of oxytocin were found in the supraoptic and the paraventricular nuclei, indicating that both are major sources of the hormone. The concentration of oxytocin in the median eminence was more than three times that in either the supraoptic or the paraventricular nuclei, and significant amounts of oxytocin were also found in the arcuate nucleus and in tow anterior hypothalamic nuclei.
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PMID:Oxytocin content of microdissected areas of rat hypothalamus. 127 9

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Using whole-cell voltage clamp of single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus, depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow [8]. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. Thus, the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels, and it is suggested that the fast Na+ current may be involved in spread of excitation. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and may facilitate parturition. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions is not due to stimulation of ICa(s). Figure 11 summarizes the possible mechanisms by which uterine contractility can be modulated. In contrast to vascular smooth muscle, neither ISO nor adenosine, which produce elevation of cyclic AMP, affected ICa and INa. Therefore, no arrow can be drawn between cA-PK/cG-PK and the Ca2+ slow channel.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus. 128 Dec 64

Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons.
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PMID:Effects of lordosis-relevant neuropeptides on midbrain periaqueductal gray neuronal activity in vitro. 128 9

Circulating concentrations of progesterone, the prostaglandin F2 alpha (PGF2 alpha), metabolite 13,14-dihydro-15-keto PGF2 alpha (DHKF2 alpha) and luteinizing hormone (LH) have been measured in cyclic ewes receiving a continuous infusion of oxytocin, in order to investigate the effect of maintained concentrations of circulating oxytocin on the luteolytic action of oestradiol-17 beta. Oxytocin (3 nmol h-1 intravenously) was given from Day 7 until Day 17 after oestrus with oestradiol-17 beta (2.76 mumol, intramuscularly in sesame oil, 0.5 mL-1) administered on Days 9 and 10. Control ewes, given a continuous infusion of saline (154 mmol L-1, 3 mL-1 h-1) and sesame oil on Days 9 and 10, underwent luteal regression at the expected time, with mean concentrations of plasma progesterone falling to below 1.5 nmol L-1 on Day 16 (0900 hours). Mean plasma progesterone concentrations fell to less than 1.5 nmol L-1 on Day 13 (0900 hours) in ewes receiving saline and oestradiol-17 beta. Oxytocin infusion delayed luteolysis in all treated ewes; those receiving oxytocin infusion and sesame oil failed to undergo luteal regression during the period studied and in animals receiving oxytocin and oestradiol-17 beta, luteolysis was significantly delayed when compared to ewes treated with saline and oestradiol with progesterone concentrations falling to < 1.5 nmol L-1 on Days 14 (n = 1 ewe), 15 (n = 1 ewe), 16 (n = 2 ewes) and > 17 (n = 2 ewes) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin delays oestradiol-induced luteolysis but does not affect oestradiol-induced luteinizing hormone secretion in the ewe. 129 35

1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1.1 +/- 0.1 spikes/s (mean +/- S.E.M.). 2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97%) were excited by 10(-6) M AVP with an increase in firing rate from the basal level of 1.1 +/- 0.1 to a maximum of 2.5 +/- 0.2 spikes/s. There was a dose-dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10(-10) M. The remaining six neurones were not affected by application of AVP. 3. Application of oxytocin (OXT, 10(-6) M) increased the firing rate of all thirty-eight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low-Ca2+ or Ca(2+)-free-high-Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes. 4. The AVP-induced excitatory responses were completely but reversibly blocked by the V1-type receptor antagonists, [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid), 2-(O-methyl)tyrosine]-arginine vasopressin (d(CH2)5Tyr(Me)AVP) (n = 5) and Phaa-D-Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly-NH2d(CH2)5[Tyr-(Me)2Thr4]ornithine vasotocin, which suppressed the OXT-induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10(-6) M) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1.0 +/- 0.1 to a maximum of 1.8 +/- 0.2 spikes/s (n = 60). The effect of AII was completely abolished by an AII receptor antagonist, [Sar1,Ile8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on AII concentration in all of eleven neurones tested. The threshold concentration was assumed to be about 10(-9) M. The activity of 5 (3%) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro. 130 79

Increased expression of the oxytocin gene of ruminants is associated with the process of luteinization both in vivo and in vitro. Cell culture studies and measurements of mRNA in luteal extracts have confirmed that the gene is switched on in the preovulatory follicle about 24 h before ovulation, at the time of the gonadotrophin surge. It is downregulated again equally rapidly after ovulation, so that by day 2 of the cycle the capacity of the luteal cells to make oxytocin has already been greatly reduced. A number of factors can increase oxytocin production by luteinizing granulosa cells. They include oestradiol and compounds such as gonadotrophins and catecholamines which are known to act by increasing intracellular concentrations of adenylyl cyclase. However, all of these factors are ineffective if the follicle is collected too early, suggesting that an initial maturation step is necessary to develop responsiveness. Analysis of the promoter region of the bovine oxytocin gene has indicated that neither oestradiol nor cAMP can directly initiate activation; instead regulation appears to occur via a COUP factor binding site. Additional transacting nuclear proteins may therefore be required to act as intermediaries. The same factors that initially stimulate oxytocin production switch to inhibiting production shortly after ovulation, leading to downregulation of the gene. After translation of oxytocin mRNA during the luteal phase, oxytocin precursor is packaged into secretory granules in the large luteal cells. Processing involves a series of enzymatic steps, culminating in amidation to produce oxytocin. Cultured cells may secrete intermediate forms of partially processed peptide, but it is not known if this also occurs in vivo. Oxytocin release from the cell involves granule exocytosis which is probably triggered by an increase in intracellular calcium. During luteolysis this is regulated by the release of prostaglandin F2 alpha (PGF2 alpha) from the uterus, although additional factors may also contribute. Neither PGF2 alpha nor catecholamines appear to be prime regulators of luteal oxytocin release during the early and mid-luteal phases of the cycle and it remains to be determined how secretion is controlled at this time.
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PMID:Control of synthesis and secretion of ovarian oxytocin in ruminants. 130 33

Oxytocin (OT) is a nine amino acid peptide synthesized in hypothalamic cells which project either to the neurohypophysis or to sites within the central nervous system. Although neurohypophyseal OT release has long been associated with uterine contraction and milk ejection, the function of intracerebral OT remains unclear. On the basis of behavioral, cellular, and comparative studies, this review suggests that brain OT influences the formation of social bonds. The first part of this review examines evidence linking central OT to several forms of affiliation. Central administration of OT induces maternal and reproductive behaviors in rats primed with gonadal steroids. OT antagonists and hypothalamic lesions block the initiation of maternal and reproductive behaviors but have no effects on these behaviors once established. Our new studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact. These studies of parental, reproductive, and attachment behaviors suggest that exogenous OT has "prosocial" effects and that endogenous OT may be essential for initiating social interaction. In a second series of experiments, we investigated the cellular mechanisms for OT's effects on social behavior by means of autoradiographic receptor binding. In the rat forebrain, OT receptors are expressed in several limbic regions believed to be involved in the integration of sensory processing. The regulation of these receptors is surprisingly resistant to either ablation of OT cells or repeated central administration of OT. However, receptors in two regions, the bed nucleus of the stria terminalis (BNST) and the ventromedial nucleus of the hypothalamus (VMN), appear selectively induced by exogenous or endogenous increases in gonadal steroids. At parturition, binding to OT receptors increases 84% in the BNST, and at estrus, binding increases 35% in the VMN. These results demonstrate that physiologic changes in gonadal steroids can alter receptor expression in anatomically discrete target fields and thereby direct responsiveness to endogenous neuropeptide release. A model for OT's effects on social behavior is proposed, which relies on the heterologous regulation of the brain OT receptor. A third series of experiments tested the hypothesis that brain OT influences affiliation by comparing prairie and montane voles, two closely related species with dichotomous systems of social organization. Although no differences appear in the presynaptic expression of the neuropeptide, OT receptors are distributed in complementary patterns in the two species. In the highly affiliative prairie vole, receptors are most evident in the BNST and one of its primary afferents, the lateral amygdala, highlighting a circuit previously implicated in maternal behavior.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Oxytocin--a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies. 131 71

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L type) Ca2+ channels and fast (T type) Ca2+ channels. Whole-cell voltage clamp was done on single smooth muscle cells isolated from the longitudinal layer of the 18-day pregnant rat uterus. Depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by tetrodotoxin (TTX) (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o (or Ba2+), and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. We conclude that the ion channels that generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells that possess fast Na+ channels. The Ca2+ channel current density was also higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and we suggest that the fast Na+ current may be involved in spread of excitation. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 = 12 mM) and nifedipine (K0.5 = 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions cannot be explained by a stimulation of ICa(s).
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PMID:Fast Na+ channels in smooth muscle from pregnant rat uterus. 132 77


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