Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Granulosa cells derived from preovulatory bovine follicles were cultured in the presence of insulin-like growth factor-I (IGF-I, 10-100 ng/ml), forskolin (10 microM), or a combination of the two agents. Forskolin alone was the most potent stimulator of both oxytocin (OT) and progesterone (P4) secretion. The two hormones had different patterns of secretion during the course of incubation. OT production peaked on Day 5 of culture and declined thereafter, whereas P4 rose gradually to a peak between Days 7 and 9. The addition of IGF-I to forskolin did not augment OT release beyond that achieved with forskolin alone, but it did maintain higher levels of OT secretion beyond the Day-5 peak. Two antisera, (antiserum I and antiserum II) directed against OT and its C-terminally extended forms, respectively, were used to identify the OT forms in culture media and granulosa cell and corpus luteum extracts. Fully processed OT was detected only in small amounts (0.43 ng/mg protein) in granulosa cell extracts, whereas the corpus luteum extracts contained 6 ng/mg protein. However, granulosa cells that had been incubated with forskolin contained stores of the OT precursor oxytocin-neurophysin, which is found in young corpora lutea. These data indicate that forskolin (whose action probably mimics gonadotropin action) is an effective stimulator of OT biosynthesis and release in cultured bovine granulosa cells.
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PMID:Biosynthesis and release of oxytocin by granulosa cells derived from preovulatory bovine follicles: effects of forskolin and insulin-like growth factor-I. 157 71

Addition of vasopressin to hypothalamo-neurohypophysial explants in vitro increased cyclic AMP accumulation whereas exogenous oxytocin decreased cyclic AMP. An opposite response pattern was observed in the neural lobe of the pituitary where vasopressin decreased and oxytocin increased cyclic AMP accumulation. Forskolin elicited a 3-fold greater increase in cyclic AMP in the neural lobe than in the supraoptic nucleus and enhanced the sensitivity of the tissues to both vasopressin and oxytocin. The ability of both vasopressin and oxytocin to modulate local cyclic AMP metabolism suggests the possibility of internal feedback within the hypothalamo-neurohypophysial system.
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PMID:Vasopressin and oxytocin regulation of cyclic AMP accumulation in rat hypothalamo-neurohypophysial explants in vitro. 216 30

Treatment of isolated rat adipocytes with epinephrine or isoproterenol caused a time- and concentration-dependent increase in phospholipid methyltransferase (PLMT) activity that was blocked by propranolol and unaffected by phentolamine. Forskolin mimicked the stimulatory effect on PLMT, and insulin inhibited this effect. In both the absence and presence of insulin, there was a linear relationship between PLMT activity and lipolysis. PLMT activity was also increased in response to oxytocin, which does not activate adenylate cyclase in adipocytes and does not stimulate lipolysis. The effects of oxytocin were inhibited by insulin and were additive with those of isoproterenol on PLMT. These data support the hypothesis that in adipocytes, PLMT is activated by a cAMP-dependent protein kinase and a cAMP-independent mechanism, both of which can be regulated independently, and both of which are sensitive to inhibition by insulin.
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PMID:Hormonal regulation of phospholipid methyltransferase by 3',5'-cyclic adenosine monophosphate-dependent and independent mechanisms. 303 90

Immediate-early genes, such as c-fos, couple extracellular signals to genetic changes in the cell. We have previously demonstrated that depolarization with 50 mM KCl increases Fos immunoreactivity in hypothalamic tyrosine hydroxylase (TH) and oxytocin immunoreactive (-ir) neurons in primary culture. This Fos activation occurs within 1.5-2 h in TH-ir cells. In the present study, we examined the effects of depolarization, glutamate receptor activation and adenylyl cyclase stimulation on Fos-ir to determine the possible mechanism(s) of Fos activation in TH-ir neurons. Hypothalamic cultures were treated with KCl, glutamate or forskolin, and Fos and TH were visualized immunocytochemically. Forskolin increased the percentage of Fos/TH-ir neurons in a dose-dependent manner, with a maximal stimulation of 53.4 +/- 4.5% Fos/TH-ir neurons at 30 microM forskolin. The dose-response curve for glutamate was steep, with a maximal stimulation of 24.8 +/- 2.1% Fos-ir neurons at 100 microM. 50 mM KCl resulted in 50.0 +/- 0.8% Fos/TH-ir neurons. Pretreatment with verapamil decreased KCl induced Fos-ir by 57%, glutamate by 65% and forskolin by 39%. Combined drug administration demonstrated significant additivity between forskolin and glutamate, and forskolin and KCl, however, no significant additivity was found with KCl and glutamate. The results are discussed in terms of cAMP and calcium mediation of the Fos response to these stimuli.
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PMID:Calcium and cAMP mediated stimulation of Fos in cultured hypothalamic tyrosine hydroxylase-immunoreactive neurons. 798 47

The marked up-regulation of oxytocin (OT) receptors in rabbit amnion at term was reproduced in cultured amnion cells by raising intracellular cAMP levels. (Bu)2AMP, forskolin, or cholera toxin caused 2- to 8-fold increases in specific binding of iodinated OT antagonist. The rise in OT receptors involves activation of protein kinase-A activity and protein synthesis, as forskolin's effects were inhibited by H-7 and H-8 and by cycloheximide, respectively. Forskolin treatment also increased specific cross-linking of a photoaffinity derivative of [125I]OT antagonist to a 50-kilodalton electrophoretic band corresponding in size to the amnion OT receptor. Forskolin and (Bu)2cAMP increased OT stimulation of prostaglandin E2 (PGE2) release; PGE2 release elicited by epidermal growth factor or calcium ionophore was unchanged. Forskolin also enhanced stimulation of PGE2 synthesis by phorbol 12-myristate 13-acetate, an activator of protein kinase-C. Because protein kinase-C mediates OT action in amnion cells, forskolin causes increases in both the signal and signal transduction mechanisms. These results suggest that cAMP mediates the exponential-like rise in rabbit amnion OT receptors occurring in vivo at term. The physiological signals increasing cAMP concentrations in amnion may be important for OT stimulation of PGE2 release and, therefore, have a significant role in the initiation and/or progression of labor.
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PMID:Up-regulation of oxytocin receptors in rabbit amnion by adenosine 3',5'-monophosphate. 838 Mar 70

Forskolin (FSK; an activator of adenylyl cyclase) and cortisol synergistically increase the concentration of oxytocin receptors (OTRs) in rabbit amnion cells. The aims of this study were to characterize potential physiological regulators of OTR concentrations acting through adenylyl cyclase and to clarify the mechanisms of potentiation by cAMP and cortisol. Both isoproterenol (ISO) and parathyroid hormone-related protein (PTHrP) elevated amnion cell cAMP levels and OTR concentrations. The effects of ISO and PTHrP on OTR were potentiated by cortisol. Cortisol had no effect on the ability of ISO or PTHrP to stimulate adenylyl cyclase activity, and cAMP did not affect the number or affinity of glucocorticoid receptors in whole cells or in cytosol. Adenylyl cyclase activation, however, caused conversion of mifepristone (RU486) from a glucocorticoid antagonist to agonist. Thus, mifepristone elevated OTR receptor concentrations in the presence of FSK. In contrast, a structurally related glucocorticoid antagonist, onapristone (ZK98 299), was unaffected by cAMP. Because glucocorticoid receptors bound to mifepristone are capable of interacting with DNA, whereas onapristone-occupied receptors are not, we conclude that cAMP affects glucocoticoid receptor-DNA interactions, accounting for the synergistic effects of cAMP and cortisol on OTRs.
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PMID:Effectors of cyclic adenosine 5'-monophosphate up-regulating-oxytocin receptors in rabbit amnion cells: isoproterenol, parathyroid hormone-related protein, and potentiation by cortisol. 852 7

The effects of arginine vasotocin (AVT) were examined in isolated gar arteries (afferent branchial, ABA; conus arteriosus, CA; ventral aorta, VA) and veins (hepatic, HV; intestinal; ovarian). AVT (10(-11) - 10(-7) M) had no effect in CA, produced contraction in ABA and VA and stimulated relaxation in veins. In precontracted HV, AVT relaxation was dose-dependent, long-lived (> 30 min) and reduced total tension by 49.0 +/- 10.7%. EC50s for AVT, arginine vasopressin, oxytocin, desmopressin, and isotocin in gar HV were 1.4 +/- 0.3, 3.6 +/- 0.2, 5.3 +/- 1.7, 11.0 +/- 6.5, and 19.0 +/- 0.4 nM, respectively. AVT was more potent compared with isotocin. Strength of relaxation (percentage decrease in total tension) of AVT and structural analogs was similar (range = 32.5 to 55%). Endothelium removal did not alter percentage relaxation or sensitivity to AVT in HV. AVT relaxation was not inhibited by nitric oxide synthase inhibitors or propranolol or reversed by addition of methylene blue but it was significantly enhanced by indomethacin (10(-5) M). Arginine vasopressin-receptor antagonists (V1- or V2-type selectivity; 10(-6) M) were equally effective inhibitors, each blocked 99% of AVT relaxation. Forskolin (10(-6) M) and papaverine (10(-4) M) relaxed precontracted gar arteries and veins. The adenylyl cyclase inhibitors SQ 22536 and MDL 12,330A (10(-5) M) produced transient contraction and stable relaxation, respectively, but did not inhibit AVT-induced relaxation in HV. Atrial natriuretic peptide (3 x 10(-8) M) and sodium nitroprusside (10(-4) M) had no effect in precontracted HV. AVT acts directly on gar venous smooth muscle cells via a nonclassical AVP receptor, possibly by increasing [cAMP]. AVT is a potent vasoconstrictor in vertebrate vasculature but produces a novel relaxation in gar veins.
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PMID:Arginine vasotocin relaxation of gar (Lepisosteous spp.) hepatic vein in vitro. 892 55

Oxytocin (OT)-stimulated PGE2 release by rabbit amnion is enhanced by the up-regulation of oxytocin receptors (OTR), which increase about 200-fold at the end of pregnancy. As recent studies have shown that PGs are essential for parturition, the rise in amnion OTR and associated PGE2 synthesis are probably essential for labor initiation. The present work was directed toward understanding the mechanisms of OTR up-regulation. Levels of agents that stimulate adenylyl cyclase activity and cortisol are increased in amniotic fluid at the end of pregnancy. Addition of either forskolin or cortisol to cultured amnion cells caused an increase in OTR ligand-binding sites and steady state OTR messenger RNA (mRNA) levels. Forskolin treatment elevated OTR mRNA levels rapidly, but transiently, whereas cortisol's effects were slower and sustained. Actinomycin or cycloheximide, added 3 h after forskolin, led to a sustained elevation in OTR mRNA levels, suggesting that forskolin increases the activities of OTR mRNA-destabilizing factors along with increasing OTR mRNA concentration. Cortisol did not appear to affect OTR mRNA stability. Measurement of OTR mRNA transcription rates showed that forskolin's effects were maximal within 1 h of treatment. In contrast, cortisol-induced transcription was not apparent until 8 h. The effects of forskolin and cortisol on OTR gene transcription were synergistic. Thus, the increase in OTR mRNA levels occurring after either forskolin or cortisol treatments is the result of induction of OTR gene expression, but the effects of the two agents appear to occur at separate sites.
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PMID:Induction of oxytocin receptor gene expression in rabbit amnion cells. 968 95

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

Abstract Vasopressin and oxytocin genes are expressed in mutually exclusive sets of magnocellular neurons in the hypothalamus. Cell specificity and regulation are probably controlled by extra- and intracellular signals acting on one or the other gene. In order to identify factors that regulate peptide expression, we have used primary dissociated cultures derived from 14-day old foetal rats. Vasopressin expression was monitored by combined immunocytochemistry and in situ hybridization. Treatment of cultures with forskolin and/or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), both of which result in elevated intracellular cyclic AMP levels, increased the numbers of vasopressin-expressing cells up to 10-fold. The specific Vasopressin messenger ribonucleic acid accumulation was verified quantitatively by ribonuclease protection assays. Forskolin and IBMX did not change the levels of the general neuronal markers, neuron-specific enolase and synaptophysin, suggesting that the effect of these drugs was specific for vasopressin-expressing cells. The drugs were not mitogenic for magnocellular neurons. Furthermore, their effect was not mediated trans-synaptically, as the drugs were also effective in cultures grown in low Ca(2+)/high Mg(2+) medium, as well as in cultures treated with either tetanus toxin or tetrodotoxin. The presence of putative response elements for the transcription factor AP-2 in the 5'promoter regions of all vasopressin genes sequenced so far may provide the molecular basis of the observed cyclic AMP effect. No such elements are present in the genes for oxytocin, the messenger ribonucleic acid levels of which were not measurably affected by forskolin and IBMX in our cultures.
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PMID:Vasopressin Expression in Cultured Neurons is Stimulated by Cyclic AMP. 1921 30


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