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)

The effects of the activation of protein kinase A (PKA), protein kinase C (PKC) and corticosteroids were investigated on the release of corticotrophin-releasing factor-41 (CRF), arginine vasopressin (AVP) and oxytocin from rat fetal hypothalamic cells in culture. Both forskolin and PMA (phorbol 12-myristate 13-acetate) increased CRF, AVP and oxytocin release, while dexamethasone and aldosterone only reduced basal secretion of CRF. Both steroids also inhibited forskolin-induced CRF, AVP and oxytocin responses to PMA. These data provide direct evidence for a role for both PKC- and PKA-mediated mechanisms in the regulation of CRF, AVP and oxytocin release and for differential effects of both glucocorticoids and mineralocorticoids on PKA- and PKC-stimulated responses.
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PMID:Release of corticotrophin-releasing factor-41, arginine vasopressin and oxytocin from rat fetal hypothalamic cells in culture: response to activation of intracellular second messengers and to corticosteroids. 173 59

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

We measured the effects of oxytocin on capacitance and hydroosmotic water flow in the urinary bladder of the toad Bufo marinus and the skins of Rana pipiens and Rana temporaria. Oxytocin increased capacitance in all these tissues but stimulated hydroosmotic water flow only in the urinary bladder. We also measured the effects of oxytocin and PMA on the capacitance and hydroosmotic water flow of the toad urinary bladder. Both agents produced increases in membrane capacitance that were additive, however, PMA produced a stimulation of water flow that was only a fraction of that caused by oxytocin. Comparison of the effects of PMA and insulin in toad urinary bladder showed that in contrast with PMA, insulin did not increase membrane capacitance in this tissue. Moreover, insulin stimulated Isc in the urinary bladder while PMA produced an inhibition of variable magnitude. These results suggest that: (1) oxytocin can promote the fusion with the apical membrane of cytoplasmic membranes with or without water channels; (2) oxytocin and PMA stimulate the fusion with the apical membrane of cytoplasmic membranes originating in different pools; membranes in each pool have different water permeabilities and their insertion is controlled by different signals; (3) PMA and insulin act through different mechanisms in the toad urinary bladder.
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PMID:Exocytotic events unrelated to regulation of water permeability in amphibian tight epithelia: effects of oxytocin, PMA and insulin on membrane capacitance, water and Na+ transport. 250 76

Two experiments were conducted to determine if the ability of oxytocin to stimulate release of prostaglandin (PG)F2 alpha from ovine uterine tissue involved activation of phospholipase C (PLC). In the first experiment, 9 ewes were injected with progesterone for 11 d (12 mg/d, im). On days 11 and 12, ewes received an injection of estradiol (100 micrograms, im). Caruncular endometrial tissue was collected on d 13 and incubated in the presence or absence of oxytocin (10(-6) M). Concentrations of PGF2 alpha and its metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), in culture media were determined by radioimmunoassay. PLC activity was determined by measuring the intracellular accumulation of 3H-inositol phosphates after preincubation with 3H-inositol. Concentrations of PGF2 alpha and total PGF (PGF2 alpha + PGFM) in culture media were greater for explants treated with oxytocin than for controls (p. less than .02, p less than .06, respectively). A similar effect of oxytocin on intracellular concentrations of 3H-inositol phosphates was observed (p less than .01). A second experiment was conducted to determine if agonists of second messengers, produced by activation of PLC, could stimulate release of PGF2 alpha from ovine endometrial tissue. Seven ewes were treated with progesterone and estradiol as in experiment 1. Explants of caruncular tissue from each ewe were incubated with 1) control medium, 2) A23187 (10(-5) M), 3) oxytocin (10(-6) M), 4) phorbol 12-myristate 13-acetate (PMA, 10(-7) M), 5) PMA + A23187 and 6) PMA + oxytocin. Significant stimulatory effects of oxytocin, PMA and A23187 on concentrations of PGF2 alpha and total PGF in culture media were observed (p. less than .05, p less than .1, p less than .1, respectively). In conclusion, oxytocin stimulated release of PGF2 alpha and activity of PLC in explants of ovine endometrial tissue in vitro. Second messengers associated with activation of PLC enhanced release of PGF2 alpha from ovine endometrial tissue.
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PMID:Role of phospholipase C in mediating oxytocin-induced release of prostaglandin F2 alpha from ovine endometrial tissue. 324 71

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

The stimulatory effect of noradrenaline (NA) as well as oxytocin (OT) on bovine endometrial prostaglandin (PG) F2alpha production, and the intracellular mechanisms of their actions, were investigated in cultured bovine endometrial cells (a mixture of epithelial, stromal, and glandular cells). The cells were cultured in Dulbecco's Modified Eagle's medium and Ham's F-12 medium (1:1 [v:v]) with 10% calf serum. When the cells reached confluence, the culture medium was replaced with fresh medium with 0.1% BSA and various doses of NA (10(-8)-10(-4) M). NA stimulated PGF2alpha production in a dose-dependent manner (p < 0.05). To evaluate the intracellular mechanisms of NA and OT actions, the cells were treated with forskolin (an activator of adenylate cyclase), phorbol 12-myristate 13-acetate (PMA, an activator of protein kinase [PK] C), Rp-cAMP (a competitive cAMP antagonist and an inhibitor of PKA), U-73122 (an inhibitor of phospholipase [PL] C), or anthranilic acid (ACA, an inhibitor of PLA2). Forskolin and PMA stimulated PGF2alpha production in a dose-dependent manner (p < 0.05). Rp-cAMP completely inhibited (p < 0.001) the NA-induced, but not the OT-induced, PGF2alpha production. Although U-73122 inhibited only OT-induced PGF2alpha production (p < 0.001), ACA completely stopped the actions of NA and OT. The overall results indicate that NA as well as OT is involved in the regulation of the endometrial PGF2alpha production in cattle and that the stimulatory effects of NA and OT on PGF2alpha production are mediated via the PKA and PKC pathways, respectively.
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PMID:Noradrenaline stimulates the production of prostaglandin f2alpha in cultured bovine endometrial cells. 991 91

Oxytocin (OT) is responsible for the episodic release of luteolytic prostaglandin (PG) F2alpha from the uterus in ruminants. The attenuation of OT-stimulated uterine PGF2alpha secretion by interferon-tau (IFN-tau) is essential for prevention of luteolysis during pregnancy in cows. To better understand the mechanisms involved, the effect of recombinant bovine IFN-tau (rbIFN-tau) on OT-induced PG production and cyclooxygenase-2 (COX-2) and PGF synthase (PGFS) expression in cultured endometrial epithelial cells was investigated. Cells were obtained from cows at Days 1-3 of the estrous cycle and cultured to confluence in RPMI medium supplemented with 5% steroid-free fetal calf serum. The cells were then incubated in the presence or absence of either 100 ng/ml OT or OT+100 ng/ml rbIFN-tau for 3, 6, 12, and 24 h. OT significantly increased PGF2alpha and PGE2 secretion at all time points (p < 0.01), while rbIFN-tau inhibited the OT-induced PG production and reduced OT receptor binding in a time-dependent manner. OT increased the steady-state level of COX-2 mRNA, measured by Northern blot, which was maximal at 3 h (9-fold increase) and then decreased with time (p < 0.01). OT also caused an increase in COX-2 protein, which peaked at 12 h (11-fold increase), as measured by Western blot. Addition of rbIFN-tau suppressed the induction of COX-2 mRNA (89%, p < 0.01) and COX-2 protein (50%, p < 0.01) by OT. OT also increased PGFS mRNA, and this stimulation was attenuated by rbIFN-tau (p < 0.01). To ensure that the decrease in COX-2 was not solely due to down-regulation of the OT receptor, cells were stimulated with a phorbol ester (phorbol 12-myristate 13-acetate; PMA) in the presence and absence of rbIFN-tau. The results showed that rbIFN-tau also decreased PMA-stimulated PG production and COX-2 protein. It can be concluded that rbIFN-tau inhibition of OT-stimulated PG production is due to down-regulation of OT receptor, COX-2, and PGFS.
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PMID:Down-regulation of oxytocin-induced cyclooxygenase-2 and prostaglandin F synthase expression by interferon-tau in bovine endometrial cells. 1002 13

Oxytocin (OT) inhibits the uptake of serotonin (5HT) into uterine mast cells. This may modulate 5HT bioavailability in the myometrium. Because 5HT isan important endogenous uterotonic compound, it has been postulated that this effect of OT may contribute to its potency as a labor inducer. This also predicts the presence of oxytocin receptors (OTRs) and transducing signals that will interact with 5HT transporters (SERT) in mast cells. In this study, OTR and SERT were characterized in murine peritoneal mast cells by radioligand-binding studies. Saturation assays for OTR showed no changes in Kd along the estrous cycle (6.95 +/- 2.76 nM in estrus and 4.07 +/- 1.73 nM in diestrus) but an increase in Bmax in estrus (0.71 +/- 0.08 pmol/10(6) cells and 0.37 +/- 0.05 pmol/10(6) cells in estrus and diestrus, respectively). Bmax and Kd for SERT were not affected along the estrous cycle. The signaling between the OTR and the SERT was analyzed by measuring the extent of inhibition of OT and PMA (activator of protein kinase C on 5HT uptake and the capability of Ro318220 (specific inhibitor of PKC) to increase 5HT uptake and block the effect of the above compounds in mast cells. The results showed that in murine peritoneal mast cells in vitro (1) ovarian hormones modulate OTR but not SERT expression, (2) the magnitude of OT action on 5HT uptake depends on the number of OTRs expressed in mast cells, and (3) the signaling between OTR and the SERT is mediated through the activation of protein kinase C. It is concluded that the ovarian hormones have a modulatory action on 5HT uptake which involves OT-mediated mechanism.
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PMID:Characterization of oxytocin receptors and serotonin transporters in mast cells. 1237 64

Adaptive responses mediated by the hypothalamus require sustained activation until homeostasis is achieved. Increases in excitatory drive to the magnocellular neuroendocrine cells that mediate these responses, however, result in the activation of a presynaptic metabotropic glutamate receptor (mGluR) that curtails synaptic excitability. Recent evidence that group III mGluRs can be inhibited by protein kinase C prompted us to test the hypothesis that activation of PKC by noradrenaline (NA) inhibits group III mGluRs and increases excitatory synaptic input to these cells. To examine the effects of NA on miniature EPSCs (mEPSCs), we obtained whole-cell recordings from magnocellular vasopressin and oxytocin neurons in the paraventricular nucleus of the hypothalamus. All of the neurons tested in the current study displayed an alpha1 adrenoceptor-mediated increase in mEPSC frequency in response to NA (1-200 microm). The excitatory effects of NA were mimicked by the phorbol ester PMA and blocked by the PKC inhibitor calphostin C. The activation of PKC inhibits the efficacy of group III mGluRs, resulting in an increase in mEPSC frequency in response to a subsequent exposure to NA. By removing feedback inhibition, this mechanism effectively primes the synapses such that subsequent activation is more efficacious. The novel form of synaptic rescaling afforded by this cross-talk between distinct metabotropic receptors provides a means by which ascending catecholamine inputs can facilitate the control of homeostasis by hypothalamic networks.
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PMID:Priming of excitatory synapses by alpha1 adrenoceptor-mediated inhibition of group III metabotropic glutamate receptors. 1286 6


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