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

This study was conducted to determine whether platelet-activating factor (PAF) (1) attenuated oxytocin-induced secretion of the prostaglandin (PG) F2 alpha metabolite, PGFM, by the ovine uterus in situ and (2) inhibited the generation of the inositol phosphate secondary messengers by endometrial tissue in response to oxytocin challenge in vitro. Ovariectomized ewes received steroid replacement to mimic the luteal phase. Six ewes received intrauterine injections of 200 micrograms PAF/uterine horn/day on Days 11-15, and 6 ewes were treated with vehicle. All ewes received 1 microgram oxytocin i.v. on Days 13-16. Pretreatment of ewes with PAF significantly suppressed PGFM release in response to oxytocin on Days 14 and 15 (p less than 0.005) compared to vehicle-treated ewes. PAF was not administered on Day 16, and the PGFM response to oxytocin was not different between groups. In a second experiment, ewes were given intrauterine injections of 200 micrograms PAF/uterine horn/day (n = 8) or vehicle (n = 7) on Days 11-15, and all ewes received 1 microgram oxytocin i.v. on Days 13 and 14. On Day 15 the uterus was removed, and the incorporation of 3H-inositol into inositol phosphates was determined in caruncular endometrium. Treatment of ewes with PAF in vivo reduced inositol monophosphate (IP1) generated by oxytocin (10(-6) M) by 56.4%, compared to that in endometrium from vehicle-treated controls, and also inhibited the incorporation of 3H-inositol into glycerophosphoinositol (GPI). If PAF was added to the endometrium during the incubation in vitro, the attenuation of inositol phosphate generation did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence that platelet-activating factor suppresses uterine oxytocin-induced 13,14-dihydro-15-keto-prostaglandin F2 alpha release and phosphatidylinositol hydrolysis in the ewe. 139 26

In previous work we reported that oxytocin activates phospholipase-C (PLC) and increases prostaglandin E2 (PGE2) release in amnion. Whether either of the consequences of activation of PLC by oxytocin, activation of protein kinase-C (PKC) or increases in intracellular calcium, directly results in the production of PGE2 is unknown. Phorbol esters (PMA) and epidermal growth factor (EGF) are also known to increase PGE2 release from amnion. In some tissues these agents are capable of activating the PLC postreceptor cascade system. This study was undertaken primarily to explore the mechanism of oxytocin-induced PGE2 production in amnion and secondarily to determine whether common aspects of PGE2 production by oxytocin, PMA, and EGF include activation of PLC or subsequent steps in this cascade followed by new mRNA/protein production. Involvement of PLC was assessed by inositol phosphate (IP1) turnover. IP1 turnover was increased by oxytocin (2.99 +/- 0.31-fold; P less than 0.01), but not by EGF or PMA. PMA inhibited oxytocin-provoked IP1 turnover (P less than 0.05). PKC involvement was initially evaluated with two PKC inhibitors, H7 and staurosporine. Each inhibited PGE2 production by oxytocin as well as that by PMA and EGF in a dose-dependent fashion. With H7, the IC50 for all agents was 5 microM; the IC50 for staurosporine was 2 nM for PMA and oxytocin and 5 nM for EGF. Agonist-induced PGE2 production was also assessed in cells in which PKC activity had been tachyphylaxed with a high concentration of PMA (400 ng/mL for 48 h). In such cells oxytocin and PMA no longer stimulated (P less than 0.001) PGE2 production, but EGF-stimulated PGE2 production was only slightly reduced. PKC involvement is, thus, implicated for oxytocin and PMA. Other enzymes that are inhibited by H7 and staurosporine are implicated in the production of PGE2 caused by EGF. Although tachyphylaxed cells produced no PGE2 with oxytocin, oxytocin increased intracellular calcium to levels higher than those seen in control cells (435 +/- 102 vs. 286 +/- 1.2) Actinomycin-D (P less than 0.001) and cycloheximide (P less than 0.05) inhibited PGE2 production caused by oxytocin, PMA, and EGF. PGE2 production by oxytocin in human amnion cells proceeds by activation of PKC, followed by new protein and mRNA production. Further, in cells without PKC, oxytocin-induced calcium transients do not increase PGE2. The ability of EGF to stimulate PGE2 in cells with no PKC activity also establishes that PKC activation is not a common intracellular step in the induction of PGE2 production by all agents.
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PMID:Protein kinase-C activation is required for oxytocin-induced prostaglandin production in human amnion cells. 202 8

The presence of inositol 1,4,5-trisphosphate (IP3) receptors in human myometrium has been investigated and their concentration compared with that of oxytocin receptors. Myometrial microsomes were incubated with 3H-IP3 alone and in the presence of unlabeled IP3. Binding was to a single class of noninteracting sites with a density of 1-2 pmol/mg of protein. The sites had characteristics of true IP3 receptors, i.e., very fast association and dissociation rates, high affinity (Kd 25-50 nM) and specificity (IP3 greater than IP3[2,4,5], IP4 much greater than IP5 greater than IP3[1,3,4], IP1, IP2, IP6), and did not metabolize 3H-IP3. The binding was maximal at pH 8, and was inhibited by calcium (IC50 = 80 nM), magnesium (IC50 = 100 microM), heparin (IC50 = 4.5 micrograms/ml), and GTP (IC50 = 150 microM). The concentration and affinity of IP3 receptors were similar in pregnant and nonpregnant myometrium and remained constant during labor. By contrast, the density of oxytocin receptor increased significantly from nonpregnant to pregnant tissue and fell in advanced spontaneous labor but not in advanced induced labor. These results provide new, additional evidence for the involvement of the phosphatidylinositol pathway in the control of uterine contractility.
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PMID:Inositol 1,4,5-trisphosphate and oxytocin binding in human myometrium. 216 8

The effects of prostaglandin F2 alpha (PGF2 alpha) on intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP) generation in human myometrial cells were evaluated and compared to the effects of oxytocin. Basal [Ca2+]i levels were 146 and 153 nM in the absence and presence of 1 mM extracellular Ca, respectively. In Ca-containing medium, both PGF2 alpha and oxytocin significantly (P less than 0.01) increased [Ca2+]i over control values, eliciting half-maximal stimulation (ED50) at 4 and 1 nM, respectively. In Ca-free medium the potency of PGF2 alpha to raise [Ca2+]i was drastically reduced (ED50, 2 microM), whereas that of oxytocin remained the same, although maximal responses were markedly decreased. PGF2 alpha had no effect on total IP production in the concentration range that significantly raised [Ca2+]i. However, at a 100 times higher concentration (10 microM), PGF2 alpha produced a maximum 48% increase in total IP, with a rapid (15-30 s) rise in IP3 and IP2, followed by IP1. A similar increase in IP production was obtained when [Ca2+]i levels were raised by A23187 to the same level as that obtained with 10-50 microM PGF2 alpha. The effect of PGF2 alpha was dependent on extracellular Ca and could be suppressed by verapamil, but not by pertussis toxin, or phorbol ester. In contrast, the potencies of oxytocin to raise IP and [Ca2+]i were similar and independent of extracellular Ca2+, and could be suppressed by pertussis toxin and phorbol ester, but not by verapamil. These data provide evidence that in isolated human myometrial cells, PGF2 alpha and oxytocin trigger an increase in [Ca2+]i by different mechanisms. The action of PGF2 alpha depends on extracellular Ca2+, whereas oxytocin activates the G-protein-dependent phospholipase-C-IP3-Ca2+ signal-transducing pathway, complemented by the influx of extracellular Ca2+.
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PMID:Regulation of intracellular free calcium in human myometrial cells by prostaglandin F2 alpha: comparison with oxytocin. 222 83

Three experiments (Exp) assessed the influence of stage of the estrous cycle, pregnancy, and intrauterine infusion of ovine conceptus secretory proteins (oCSP) on turnover of inositol trisphosphate (the putative second-messenger for oxytocin-stimulated secretion of prostaglandin F2 alpha) in ovine endometrium during luteolysis and maternal recognition of pregnancy. In Exp 1, endometrium was collected from 5 cyclic (Cy) and 6 pregnant (P) ewes on Day 16 after onset of estrus. In Exp 2, endometrium was collected from Day 12 Cy (n = 5), Day 12 P (n = 3), Day 16 Cy (n = 4), and Day 16 P (n = 3) ewes. In Exp 3, 12 Cy ewes were allotted randomly, in a 2 x 2 factorial arrangement, to receive serum protein (SP), or oCSP and estradiol-17 beta (E2), or vehicle treatments. Ewes were injected i.v. with 0.5 mg E2 or vehicle on Day 12 and received twice-daily infusions of 1.5 mg SP or oCSP (containing 25 micrograms ovine trophoblast protein-1 by radioimmunoassay [RIA]) + SP (1.5 mg total protein) into each uterine horn on Days 12, 13, and 14. Blood samples for RIA of plasma progesterone were collected on Days 10-15 (before treatment on each day) and endometrium was collected on Day 15. For each Exp, 100 mg endometrium was incubated, in duplicate, for 2 h with 10 microCi [3H] inositol and treated with 0 or 100 nM oxytocin (OT) for 20 min, then [3H]inositol mono-, bis-, and trisphosphates (IP1, IP2, and IP3, respectively) were quantified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin-stimulated inositol phosphate turnover in endometrium of ewes is influenced by stage of the estrous cycle, pregnancy, and intrauterine infusion of ovine conceptus secretory proteins. 231 Aug 21

In the guinea pig myometrium prelabelled with myo-[2-3H]inositol, carbachol and oxytocin enhanced a concentration-dependent and rapid release of IP3 which preceded that of IP2 and IP1. The specific receptor-mediated phospholipase C activation degrading PIP2 to IP3 did not require the presence of extracellular Ca2+. The ionophore A23187 as well as K+ depolarization failed to increase inositol phosphate accumulation. It is proposed that IP3 could have a role in the contraction of uterine smooth muscle elicited by the activation of muscarinic as well as of oxytocin receptors.
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PMID:Carbachol and oxytocin stimulate the generation of inositol phosphates in the guinea pig myometrium. 301 7

In oxytocin (OT)-induced myometrial contraction, it is considered that Ca2+ release associated with activation of PI response is the main cascade. Steroid hormones such as dehydroepiandrosterone-sulfate (DHAS), progesterone (P), and cortisol (F), which show diverse changes during pregnancy, are considered to be involved in myometrial contraction at the onset of delivery. In this study, we examined changes in the intracellular Ca2+ concentration ([Ca2+]i) and PI response under OT stimulation. (1) After cultured human myometrial cells were incubated for 48 hours in a medium containing 10(-6) M of DHAS, P, or F, [Ca2+]i was measured with an OLYMPUS OSP3 by using the fluorescent Ca2+ indicator Fura2-AM. When the maximum change in [Ca2+]i under stimulation with 10(-8) M OT was regarded as 100% (control), it was increased significantly to 121.1 +/- 9.8% in the cells treated with F, but was reduced to 89.4 +/- 4% in those treated with P. It was increased to 107.5 +/- 6.9% in the cells treated with DHAS, but the difference was not significant. (2) After loading with 5 microCi 3H myo-inositol and various steroid hormones for 24 hours in the cells, the intracellular IP1-3 production under stimulation with 10(-8) M OT was examined. IP1-3 production and IP total production (IPn) were significantly increased in the cells treated with F as compared with the control, but IPn was reduced by about 40% in the cells treated with 10(-6) M P. And in the cells treated with DHAS, IPn was slightly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of steroid hormones on change in [Ca2+]i and on PI response following oxytocin stimulation in cultured human myometrial cells]. 770 62

We recently demonstrated that the neural peptide vasopressin (AVP) can act as a neurotrophic factor for hippocampal nerve cells in culture. Because the neurotrophic effect of vasopressin is mediated by the V1 receptor, we investigated AVP activation of calcium signaling pathways in cultured hippocampal neurons. Results of this investigation demonstrate that exposure of cultured hippocampal neurons prelabeled with [3H]myo-inositol to vasopressin induced a significant accumulation of [3H]inositol-1-phosphate ([3H]IP1). The selective V1 vasopressin receptor agonist, [Phe2, Orn2]vasotocin, induced a significant accumulation of [3H]IP1 whereas a selective V2 vasopressin receptor agonist, [deamino1, D-Arg8]-vasopressin, did not. Moreover, V1 agonist-induced accumulation of [3H]IP1 was blocked by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 agonist-induced accumulation of [3H]IP1 was concentration dependent and exhibited a steep inverted U-shaped curve that included both stimulation and inhibition of [3H]IP1 accumulation. Time course analysis of V1 agonist-induced accumulation of [3H]IP1 revealed significant increase by 20 min which continued to be significantly elevated for 60 min. Investigation of the effect of closely related peptides on [3H]IP1 accumulation indicated that the vasopressin metabolite peptide AVP4-9 and oxytocin significantly increased [3H]IP1 accumulation whereas the vasopressin metabolite peptide AVP4-8 did not. AVP4-9 and oxytocin induced [3H]IP1 accumulation were blocked by the V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 receptor activation was associated with a pronounced rise in intracellular calcium. Results of calcium fluorometry studies indicated that V1 agonist exposure induced a marked and sustained rise in intracellular calcium that exhibited oscillations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin-induced calcium signaling in cultured hippocampal neurons. 789 79

We recently demonstrated that the neural peptide vasopressin (AVP) can act as a neurotrophic factor for hippocampal nerve cells in culture. Because the neurotrophic effect of vasopressin is mediated by the V1 receptor [11], we investigated AVP activation of calcium signaling pathways in cultured hippocampal neurons. Results of this investigation demonstrate that exposure of cultured hippocampal neurons prelabeled with [3H]myo-inositol to vasopressin induced a significant accumulation of [3H]inositol-1-phosphate ([3H]IP1). The selective V1 vasopressin receptor agonist, [Phe2, Orn2]vasotocin, induced a significant accumulation of [3H]IP1 whereas a selective V2 vasopressin receptor agonist, [deamino1, D-Arg8]-vasopressin, did not. Moreover, V1 agonist-induced accumulation of [3H]IP1 was blocked by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 agonist-induced accumulation of [3H]IP1 was concentration dependent and exhibited a steep inverted U-shaped curve that included both stimulation and inhibition of [3H]IP1 accumulation. Time course analysis of V1 agonist-induced accumulation of [3H]IP1 revealed significant increase by 20 min which continued to be significantly elevated for 60 min. Investigation of the effect of closely related peptides on [3H]IP1 accumulation indicated that the vasopressin metabolite peptide AVP4-9 and oxytocin significantly increased [3H]IP1 accumulation whereas the vasopressin metabolite peptide AVP4-8 did not. AVP4-9 and oxytocin induced [3H]IP1 accumulation were blocked by the V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 receptor activation was associated with a pronounced rise in intracellular calcium. Results of calcium fluorometry studies indicated that V1 agonist exposure induced a marked and sustained rise in intracellular calcium that exhibited oscillations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin-induced calcium signaling in cultured hippocampal neurons. 783 78

The aim of this study was to investigate the effects of hCG, hCG plus oxytocin and oxytocin on [3H] inositol phosphate (IP) formations in porcine myometrial cells obtained from ovariectomized and cyclic gilts. Myometrial cells were treated with radioactive myo-[3H]inositol for 48 hours, washed and pre-incubated with 10 mM LiCl, and then different doses of hCG (10, 100, 1000 mU) were added over 24 h. At the end of the last day of culture some wells were treated with 1 microM oxytocin for 30 min. The highest production of total inositol phosphates (d.p.m.) was found in cells from ovariectomized gilts given in vivo estradiol benzoate and progesterone for five consecutive days and treated with 1000 mU hCG and 100 mU hCG plus 1 microM oxytocin (984 +/- 84 and 1063 +/- 131 vs 314 +/- 36, respectively). There was also a very significant increase of IP1 after the addition of 1000 mU hCG (p < 0.001) and IP1 and IP3 when 1000 mU hCG plus oxytocin were added (p < 0.001 and p < 0.01, respectively). Myometrial cells harvested from ovariectomized, untreated in vivo, gilts did not respond to both oxytocin and hCG in vitro. Only oxytocin alone increased the formation of IPs in cells from ovariectomized pigs treated with estradiol in vivo (p < 0.01). Myometrial cells obtained from cyclic pigs during the luteal and follicular phases of the estrous cycle responded to lower doses of hCG (10 mU), causing significant production of IPs (p < 0.05). The highest dose of hCG plus oxytocin provoked accumulation of total [3H]inositol phosphate (p < 0.05) 53% over the basal level on days 21/1 of the estrous cycle. The present study demonstrates that hCG and oxytocin can increase the accumulation of inositol phosphates in porcine myometrial cells. However, this formation is dependent on the steroid hormone status of animals.
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PMID:The effect of oxytocin on hCG action in phosphoinositide turnover in porcine myometrial smooth muscle cells. 852 14


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