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

In the ruminant ovary, synthesis and secretion of oxytocin begin in the granulosa cells of the preovulatory follicle and are markedly stimulated by the surge of LH and FSH. Luteinization of the granulosa cells results in a further increase in oxytocin gene expression, but translation of mRNA appears to be retarded because the peak concentration of luteal oxytocin occurs later than the maximal accumulation of the message. Several hormones have been shown to stimulate oxytocin secretion from granulosa and luteal cells in vivo or in vitro. However, the role of prostaglandin F2 alpha (PGF2 alpha) in regulating luteal oxytocin secretion has perhaps received more study than other hormones. The mechanism of action of PGF2 alpha has been shown to encompass a phosphoinositide cascade and activation of protein kinase C, events that are associated with luteal secretion of oxytocin. Protein kinase C phosphorylation of the actin-binding protein myristolated alanine-rich C kinase substrate (MARCKS) may be required for exocytosis of oxytocin.
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PMID:Dynamics of molecular mechanisms underlying ovarian oxytocin secretion. 762 28

The role of oestradiol in the control of uterine responsiveness to oxytocin was investigated by measuring oxytocin-induced phospholipase C activation in [3H]inositol-labelled cultured human myometrial cells. Addition of oestradiol to steroid-free culture medium (10% (v/v) fetal calf serum treated with dextran-coated charcoal in phenol red-free medium) enhanced formation of inositol phosphates and this effect was completely abolished by the anti-oestrogen tamoxifen. The inhibitory effect of tamoxifen on oxytocin-induced phospholipase C activation occurred in both steroid-free and complete culture medium; it was time- and concentration-dependent and was only partly reversed by oestradiol. When phospholipase C was activated with PGF2 alpha or fluoroaluminate instead of oxytocin, oestradiol and tamoxifen had the same stimulatory and inhibitory effects, respectively. The inhibitory effect of tamoxifen could not be prevented by treating the cells with pertussis toxin. Moreover, the effect of tamoxifen was not mediated by inhibition of protein kinase C, since the use of staurosporine (a protein kinase inhibitor) resulted in potentiation of phospholipase C activation by oxytocin. Both oestradiol and tamoxifen increased [3H]inositol incorporation into cellular lipids and cell proliferation. These results suggest that oestradiol enhances myometrial responsiveness to oxytocin and other agonists by facilitating phospholipase C activation at a post-receptor level. This effect is antagonized by tamoxifen; however, tamoxifen also has oestrogen-independent inhibitory effects.
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PMID:Effects of oestradiol and tamoxifen on oxytocin-induced phospholipase C activation in human myometrial cells. 770 87

It has been postulated that hormonal signal acts upon decidua and ammion to trigger labor via production of PGs. In our experiment the decidua cells of pregnant rats (day 19) were digested and dispersed to test the effect of oxytocin on intracellular calcium ion concentration [Ca2+]i which was measured with the fluorescent dye fura-2. Addition of oxytocin 0.001-1 mumol.L-1 to the test system resulted in a dose-dependent transient increase in [Ca2+]i which peaked within 15 s and returned to base line in 12 min. Repeated addition of oxytocin 1 mumol.L-1 failed to elicit a repeated response. In the decidua cells of dihydroepiandroterone sulfate-treated pregnant rats, the [Ca2+]i peak provoked by oxytocin was significantly higher than in the controls. These results suggest that oxytocin may activate the inositol-phospholipid-protein kinase C effector system in decidua cells of pregnant rats. Dihydroepiandrosterone sulfate may influence the action.
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PMID:[Oxytocin provoke intracellular calcium ion concentration in dispersed decidua cells of late pregnant rats]. 786 82

Cultured astroglial cells obtained from rat fetal hypothalamus express oxytocin (OT) receptors, which have been previously characterized (Di Scala-Guenot and Strosser. Biochem. J. 284: 491-497, 1992), with a radioiodinated OT antagonist. In these cells, at steady-state binding at 37 degrees C, ice-cold acidic treatment released 10% of the bound ligand; with pronase treatment, 52% of the tracer was released. Because the binding was performed with an antagonist, one could assume that the radiolabeled ligand remains locked into the membrane in a state insensitive to the stripping agents rather than being internalized. Receptor downregulation induced by OT was concentration- and time-dependent, leading to a 72% loss of maximal binding capacity without changing the affinity of the receptor. On removal of OT the binding capacity recovered partially and the restoration process was blocked by monensin (20 microM) but not by cycloheximide (20 micrograms/ml), suggesting involvement of receptor recycling. Concerning the early mechanisms involved in the downregulation processes, uncoupling of the receptor from the G protein and the receptor phosphorylation by protein kinase C could be demonstrated. Treatment of the cells with the OT antagonist d(CH2)5OVT was shown to facilitate radioligand binding and to protect the receptor against OT-induced downregulation.
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PMID:Downregulation of the oxytocin receptor on cultured astroglial cells. 786 80

N-Methyl-D-Aspartate(NMDA)-sensitive glutamate receptors, are critically involved in the induction of the learning process. Activation of NMDA receptors by glutamate lead to massive influx of extracellular Ca2+, with ensuing activation of a variety of Ca(2+)-dependent enzymes, including protein kinase C. This triggers a cascade of intracellular reactions which is essential for memory formation. In culture neurons, high concentrations of oxytocin (> 1 microM) attenuate the stimulation of 45Ca2+ influx promoted by glutamate through the activation NMDA receptors. In addition, the hormone reduces glutamate-stimulated [3H]4-beta-phorbol 12,13-dibutyrate (PdBu) binding in intact cells, a parameter that reflects the translocation of protein kinase C from the cytosol to the cell membrane. Taken collectively, these results indicate that oxytocin reduces the activity of NMDA receptors, thus impairing one of the major substrates for the induction of learning and memory.
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PMID:Oxytocin reduces the activity of N-methyl-D-aspartate receptors in cultured neurons. 790

High concentrations of PGF2 alpha and PGE2 are produced by the uterus during the early postpartum period in cows and may play an important role in both placental separation and uterine involution. In the present study, we have examined the hormonal and intracellular control mechanisms involved in PGF2 alpha and PGE2 secretion by caruncular and allantochorionic tissue in vitro. Tissue explants, obtained about 6 hr postpartum from cows that delivered normally (NFM, n = 10) or cows with retained fetal membranes (RFM, n = 4), were incubated for 6 hr and PGF2 alpha and PGE2 concentrations in the medium were determined by radioimmunoassay. Addition of oxytocin (100 microU/ml), platelet activating factor (PAF, 100 ng/ml) and epidermal growth factor (EGF, 100 ng/ml) had no effect on secretion of PGF2 alpha from the caruncle, but oxytocin and PAF did stimulate PGE2. There was no difference between groups of cows. All three substances stimulated PGF2 alpha from the allantochorion of NFM, but not RFM, cows and stimulated PGE2 secretion from the allantochorion of both groups of cows. Incubation of the tissues with cholera toxin (100 ng/ml), dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cAMP, 1 mM), calcium ionophore A23187 (5 microM) or phorbol ester 12-myristate-13 acetate (PMA, 100 nM) showed that PGF2 alpha secretion is essentially via the calcium-protein kinase C effector pathway. However, calcium-protein kinase C and cAMP second messenger systems appear to be involved in the secretion of PGE2. Prostaglandin secretion was sensitive to cycloheximide in both caruncular and allantochorionic tissues, suggesting that protein synthesis may be involved. In conclusion, these data show that in vitro PGF2 alpha secretion can be modulated by the agonists used only in allantochorion and is essentially via the calcium-protein kinase C effector pathway. PGE2 secretion can be modified in both caruncular and allantochorion tissues and involves both inositol triphosphate-diacylglycerol and cAMP second messenger systems.
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PMID:Control of in vitro prostaglandin F2 alpha and E2 synthesis by caruncular and allantochorionic tissues from cows that calved normally and those with retained fetal membranes. 804 99

Effects of phenylephrine, oxytocin and angiotensin on fructose 2,6-bisphosphate (Fru 2,6-P2) content and glycolytic parameters were studied in incubated thymus lymphocytes. These hormones modified Fru 2,6-P2 content dependent upon the energetic status of the cells. In non-preincubated thymus lymphocytes (with relatively high levels of glycogen and ATP), phenylephrine, oxytocin and angiotensin depressed Fru 2,6-P2 content in a dose-dependent manner. The opposite was found when the cells were preincubated for 2 h without substrates (low levels of ATP and glycogen). Changes in lactate release were less evident, but significant. Phenylephrine did not modify the maximal activities of phosphofructokinase (PFK)-1 or PFK-2. However, both submaximal PFK-1 and PFK-2 activities were inhibited by phenylephrine, and the response to exogenous Fru 2,6-P2 on PFK-1 was also altered. The activities of Fru 1,6-P2 and pyruvate kinase were not modified by phenylephrine or A23187 treatment. Simultaneous presence of Cyclosporin A (CsA), an immunosuppressive drug, antagonizes the alpha-adrenergic effect on Fru 2,6-P2 content. CsA alone did not alter basal levels of ATP, hexose phosphate or Fru 2,6-P2, and its opposing effect to alpha-agonist was dose-dependent. CsA cannot change the positive action of PMA or the negative action of A23187 on Fru 2,6-P2 content. The present data suggest that CsA acts prior to calcium liberation and protein kinase C activation. Different possible molecular models are discussed.
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PMID:Cyclosporin A antagonizes phenylephrine, oxytocin and angiotensin effects on glucose metabolism in rat thymus lymphocytes. 814 99

One of the roles previously reported for protein kinase C (PKC) is modulation of the activity of the phosphatidylinositol signaling pathway. Studies were performed to test the hypothesis that activation of PKC results in inhibition of agonist-stimulated phasic myometrial contractions: contractions that appear to be mediated by phosphatidylinositol signaling mechanisms comparable to those producing cytosolic calcium oscillations. In vitro isometric contraction studies were performed using myometrium from adult Sprague-Dawley rats. Oxytocin and aluminium fluoride (a G-protein activator) produced comparable increases in phasic contractile activity. Phorbol 12,13-dibutyrate (PDB) significantly suppressed agonist-stimulated phasic myometrial contractions; in contrast, phorbol 13,20-diacetate (PDA), an inactive phorbol ester, had no significant effect on myometrial contractions. Prolonged exposure of myometrial tissue to PDB failed to down-regulate myometrial PKC and had no consistent effect on spontaneous and oxytocin-stimulated phasic contractions. These studies have provided support for a role for PKC as an intracellular regulator of the phosphatidylinositol signaling pathway, which itself appears to be part of the myometrial calcium oscillator that results in agonist-stimulated phasic myometrial contractions.
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PMID:Protein kinase C, an inhibitor of oxytocin-stimulated phasic myometrial contractions. 819 66

The bovine CL is one of the sites for the production of prostaglandins (PG). Although many in vitro models, mainly using dispersed luteal cell incubations, have shown the variety of CL responses to PGs (luteotropic, no effect, or luteolytic), the functional role of luteal PGs in cattle remains to be elucidated. Therefore, the aim of the present study was to examine the effects of PGs with respect to progesterone (P4) and oxytocin (OT) release from the bovine CL in vitro (Days 8-12 of the estrous cycle) via a microdialysis system (MDS), in which intact cell-to-cell contact exists. Thirty-minute perfusion with PGF2 alpha, PGE2, and PGI2 (10(-10)-10(-5) M) induced significant, but different, acute effects. PGF2 alpha and PGE2 clearly stimulated hormone (P4 and OT) release, while PGI2 slightly inhibited hormone secretion during infusion at low doses but stimulated secretion at 10(-6) and 10(-5) M concentrations. Additionally, catabolized PGF2 alpha and PGI2 (13,14-dihydro-15-keto-PGF2 alpha [PGFM] and 6-keto-PGF1 alpha, respectively) induced responses different from those of the original PGs; both PGFM and 6-keto-PGF1 alpha at low doses weakly inhibited P4 release, but at 10(-5) M concentration stimulated release. Phorbol 12-myristate 13-acetate (TPA), a potent stimulator of the protein kinase C (PKC) system in bovine luteal cells, stimulated P4 and OT release when administered alone. Pre-exposure with TPA (10(-9) M) for 2.5 h resulted in an increase in the stimulative potency of PGF2 alpha and PGI2, but not of PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute actions of prostaglandin F2 alpha, E2, and I2 in microdialyzed bovine corpus luteum in vitro. 837 69

The effect of the activator, phorbol 12,13-dibutyrate (PDB), and the inhibitor, H-7, of protein kinase C (PKC) has been assayed in rat uterus. PDB increases the amplitude of spontaneous contractions of rat uterus and this effect does not occur in the presence of H-7 or nifedipine. PDB did not modify the KCl-induced tonic contraction but H-7 relaxed it, in a concentration-dependent way. PDB inhibited the contraction induced by oxytocin in rat uterus incubated in Ca-free solution and relaxed the tonic contraction induced by oxytocin in this medium. The relaxing effect of PDB on oxytocin-induced contraction was not modified by H-7. Thus H-7 relaxed, in a concentration-dependent way, the tonic contractions induced by oxytocin and vanadate in the rat uterus incubated in Ca-free medium. Our results suggest a dual effect of PDB related to calcium, and a direct and PKC-independent inhibitory effect of H-7.
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PMID:Effects of phorbol 12,13-dibutyrate and H-7 in extravascular smooth muscle contraction. 841 65


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