Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of arachidonic acid (AA) by caruncular and allantochorionic tissues and its regulation was studied in normal cows (n = 13) and those with retained fetal membranes (RFM; n = 9). Tissues were taken via the vagina about 6 hours postpartum and incubated for 6 hours in minimum essential medium containing tritiated AA alone or in the presence of oxytocin, platelet activating factor (PAF), epidermal growth factor (EGF) or ionophore calcium (A23187). The metabolites of AA were separated by reverse phase-high pressure-liquid chromatography. Tissue concentrations of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) and plasma 13,14-dihydro-15-keto-PGF2 alpha (PGFM) concentration were also measured by radioimmunoassay. For caruncular tissue, less thromboxane B2 (TXB2) and more 6-keto prostaglandin F1 alpha (PGIM) was synthesized in tissue from the animals with RFM than in the controls. Oxytocin, PAF, EGF and A23187 increased only PGIM production in the control animals; A23187 also decreased TBX2 synthesis. For the allantochorion, more PGE2, leukotriene B4 (LTB4) and PGIM and less TXB2, PGF2 alpha and hydroxyecosatetranoic acids (HETE) was synthesized in tissue from cows with RFM than from animals that delivered normally. All of the substances used in this study increased PGIM, PGF2 alpha and LTB4 and decreased TXB2 production by the allantochorionic tissue in control animals. The metabolism of AA by the allantochorionic tissue seems quantitatively under hormonal control. The metabolism of AA at the level of both maternal and fetal components of the placenta in cows with RFM differed from that seen in animals that expelled the membranes normally.
 ...
PMID:Metabolism of arachidonic acid by caruncular and allantochorionic tissues in cows with retained fetal membranes (RFM). 838 Sep 36

Prostaglandin (PG) production by human amnion has been postulated to have a role in the onset of labor. Previous work by ourselves and others has demonstrated that oxytocin, phorbol esters and epidermal growth factor (EGF) increase PGE2 production in human amnion cells by activation of the Phospholipase C/Protein Kinase C (PKC) cascade system. The present study was undertaken to determine the effect of prior activation of the Adenylate Cyclase cascade system upon subsequent stimulation of PGE2 production by oxytocin, phorbol 12-myristate-13-acetate (PMA) or EGF in amnion cells and membrane discs. Isoproterenol, forskolin and dibutyryl cyclic adenosine monophosphate (dbcAMP) were utilized to activate the Adenylate Cyclase system at the receptor, enzyme and second messenger level. In control amnion cells, oxytocin, PMA and EGF each provoked dose dependent increases in PGE2 production. In cells preincubated with dbcAMP, forskolin or isoproterenol, agonist stimulated PGE2 production was markedly (50-90%) inhibited (p < 0.01). Inhibition was dose dependent upon preincubator concentrations. Maximal inhibition by adenylate cyclase activators occurred with 2-4 h of preincubation. In membrane discs, forskolin preincubation also inhibited oxytocin, PMA and EGF stimulation of PGE2 production. Activation of the Adenylate Cyclase system in human amnion cells or membrane discs inhibits the subsequent action of potent stimulators of PGE2 production in human amnion.
 ...
PMID:Protein kinase A activators inhibit agonist induced prostaglandin production in human amnion. 839 7

We investigated the activity of phospholipase D (PLD) in human amnion cells labeled with [3H]oleate. The PLD activity was detected as signal-induced synthesis of phosphatidic acid (PA) and in the presence of ethanol, phosphatidylethanol (PEt). The PLD was shown to be activated by phorbol, 12-myristate, 13-acetate (PMA), calcium ionophore A23187, oxytocin, bombesin and bradykinin, but not by platelet-activating factor (PAF) and epidermal growth factor (EGF). The amniotic PLD thus appeared to be activated by a variety of agonists but with a certain specificity to stimulators. We examined the mode of the PLD activation using PMA (20 nM) and bradykinin (1 microM) as model stimulators. PMA and bradykinin elicited a rapid and sustained response with the peaks of PA-labeling attained at 5 and < 1 min after stimulation, respectively. In both cases, there was a concomitant rise of diacylglycerol (DG), and the PA accumulation was suppressed by ethanol at the expense of labeling of PEt. The PA synthesis caused by the two stimulators was similarly inhibited by staurosporine and by a chronic treatment with PMA (100 nM for 24 h), suggesting that the activation of PLD is linked to the action of protein kinase C. With the cells labeled with radioactive choline and ethanolamine, we found that the amniotic PLD hydrolyzed almost equally phosphatidylcholine and phosphatidylethanolamine. Although bradykinin and PMA stimulated cellular PLD to a comparable extent, prostaglandin (PG)E2 release was not stimulated by bradykinin in contrast to the marked effect by PMA. Further work is thus needed to clarify the significance of the novel PLD signaling pathway in the function of amnion cells.
 ...
PMID:Phospholipase D activity of human amnion cells stimulated with phorbol ester and bradykinin. 850 57

The thermolabile large T-antigen, encoded by the simian virus 40 early region mutant tsA58, was used to establish clonal cell lines (BMM-UV) from primary bovine myoepithelial cells. The BMM-UV cells have undergone more than 300 population doublings without any signs of senescence, and they contain the intranuclear large T antigen. At low confluency, they grow in a spindlelike manner and develop very long projections that most likely allow for communication of cells at a distance from each other. Establishment results in a decrease in the number of cells that contract in response to oxytocin compared with the parental nontransfected cells (20% versus 45%). Oxytocin responsiveness of BMM-UV cells increases when the cells are cultured in a medium supplemented with staphylococcal proteases. Proliferation of BMM-UV cells increases when they are cultured in the presence of epidermal growth factor (10 ng/ml) or insulinlike growth factor I (50 ng/ml). The BMM-UV cells may become a useful model to study growth properties, cell-to-cell communication, and the function of bovine mammary myoepithelial cells.
 ...
PMID:Establishment and characterization of a bovine mammary myoepithelial cell line. 892 37

The objective of this study was to investigate the mechanism of action of PGF2 alpha in cultured human myometrial cells. We measured the effects of PGF2 alpha and fluprostenol, a selective PGF2 alpha receptor (FP receptor) agonist, on phospholipase C(PLC) activation, on changes in the intracellular free calcium concentration ([Ca2+]i), and on protein tyrosine phosphorylation. PGF2 alpha and fluprostenol activated PLC (determined by measuring the formation of inositol phosphates) and increased [Ca2+]i in a concentration-dependent manner. The apparent affinity of the FP receptor for fluprostenol was higher than that for PGF2 alpha when measuring PLC activation, but the receptor displayed similar affinities for both agonists when measuring increases in [Ca2+]i. These effects were not altered by treating the cells with pertussis toxin (PT), suggesting that the FP receptor is linked to PLC activation by a G protein of the Gq family. By contrast, the effect of oxytocin on PLC activation involved both PT-resistant and PT-sensitive pathways. Human myometrial cells responded to pervanadate and epidermal growth factor with increased PLC activity and increased tyrosine phosphorylation, demonstrating a functional PLC-gamma tyrosine kinase pathway. However, neither fluprostenol nor oxytocin stimulated tyrosine phosphorylation, but the effects of both agonists were inhibited after protein kinase C stimulation. These data suggest that fluprostenol and oxytocin activate PLC-beta rather than PLC-gamma isoforms. The effect of fluprostenol is Ca2+ dependent, but is unlikely to involve a direct effect of Ca2+ on PLC activity.
 ...
PMID:Fluprostenol activates phospholipase C and Ca2+ mobilization in human myometrial cells. 896 35

The present studies were designed to examine the regulation of leptin release in primary cultures of adipocytes from fed hypothyroid rats incubated with hormones for 24 hours. Leptin release was increased in the presence of dexamethasone, while the decrease in leptin mRNA content over a 24-hour incubation was reduced by dexamethasone. Dexamethasone did not affect the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA or 18S RNA content of adipocytes. Insulin increased leptin release by adipocytes in both the absence and presence of dexamethasone. Although insulin also prevented the loss of leptin mRNA, this effect was less than that observed for GAPDH mRNA or 18S RNA content. In isolated adipocytes, the loss of almost half the 18S RNA content over a 24-hour incubation was prevented in the presence of insulin but not oxytocin or epidermal growth factor (EGF). The specific beta3 catecholamine agonist CI 316,243 inhibited the effects of dexamethasone on leptin release and leptin mRNA accumulation, as did EGF, without affecting 18S RNA content. Oxytocin inhibited the increase in leptin release due to dexamethasone without affecting leptin mRNA levels. These data indicate that although dexamethasone and insulin are positive regulators of leptin release, only dexamethasone specifically prevented the loss of leptin mRNA in cultured rat adipocytes. In contrast, insulin, but not dexamethasone, prevented the marked loss in 18S RNA observed over a 24-hour incubation of rat adipocytes.
 ...
PMID:Hormonal regulation of 18S RNA, leptin mRNA, and leptin release in adipocytes from hypothyroid rats. 986 73

1. Endothelin (ET) and its mRNA are present in endometrium. Expression of ET varies across the menstrual cycle, reaching maximal levels in the premenstrual phase, suggesting a paracrine role in endometrial bleeding and/or repair. 2. The major cellular source of ET is the epithelium, although endothelium and decidualized stroma are additional sites of production. Epithelial ET is the ET-1 isoform and this is able to contract rat thoracic aortic rings ex vivo. 3. Endothelin-1 production by cultured endometrial epithelial cells is markedly increased by serum and, to a lesser extent, by transforming growth factor-beta and interleukin-1 alpha, but not by epidermal growth factor, oxytocin, arginine vasopressin, thrombin or angiotensin II, which stimulate ET production in other tissues. 4. Endothelin-1 has mitogenic actions on endometrial stromal cells; it stimulates the uptake of [3H]-thymidine, acting via the AP-1 cis element c-jun. 5. Neutral endopeptidase (NEP), a membrane-bound ectoenzyme that is capable of degrading ET, is localized principally in endometrial stroma and immunoreactivity is maximal in the secretory phase of the cycle. 6. A potential role for ET in regulating endometrial bleeding is suggested by studies on endometrium from two groups of women who were experiencing abnormal uterine bleeding: users of the contraceptive Norplant (Leiras Co., Turku, Finland) and subjects with documented menorrhagia. In both groups, ET-1 immunoreactivity in endometrial epithelium was markedly reduced compared with the normal menstrual cycle and did not vary cyclically, while NEP immunoreactivity, particularly in the epithelium, was increased. Thus, ET may be involved in endometrial bleeding, as a vasoconstrictor before the onset of menstruation when vasoconstriction is intense and, subsequently, when it may be required in the cessation of menstrual bleeding. Furthermore, the mitogenic actions of ET may play a role in endometrial regeneration and remodelling during the menstrual cycle, particularly following menstruation.
 ...
PMID:Endometrial endothelin: regulator of uterine bleeding and endometrial repair. 1006 38

Oxygen free radicals have been suggested to play important roles in atherogenesis and other pathological processes in the blood vessel wall. The vascular wall contains large amounts of extracellular superoxide dismutase (EC-SOD), which is produced and secreted to the extracellular space by smooth muscle cells. In this study, we investigated the influence of factors regulating tension and proliferation of vascular smooth muscle cells and of some interstitial matrix components on EC-SOD expression. The expression and secretion of EC-SOD were upregulated by histamine, vasopressin, oxytocin, endothelin-1, angiotensin II, serotonin, heparin, and heparan sulfate and were downregulated by platelet-derived growth factors-AA and -BB, acidic and basic fibroblast growth factors, and epidermal growth factor. The responses were slow and developed over several days. The findings suggest that various physiological and pathological conditions might markedly influence EC-SOD expression, significantly altering the susceptibility of the vascular wall to effects of the superoxide radical.
 ...
PMID:Vasoactive factors and growth factors alter vascular smooth muscle cell EC-SOD expression. 1155 52

The increased expression of contraction-associated proteins, including oxytocin receptors, connexin-43, and prostaglandin F2alpha receptors, in term pregnant myometrium is classically considered to be the concrete expression of myometrial activation. However, the decrease in prostaglandin E2 receptor subtype EP2 on one hand and the down-regulation of the nitric oxide (NO) pathway and various vasorelaxing peptides on the other hand probably also play a key role in the loss of quiescence, and, with the above-mentioned activation, in the maturation of the myometrium. Decidual activation and production of interleukin-1, tumour necrosis factor-alpha and epidermal growth factor enhance prostaglandin production in both the amnion and chorion, and also in the myometrium. A substantial increase of eicosanoids concentration in myometrial tissue is probably an important condition for the success of the ultimate step of myometrial stimulation and the onset of labour. During labour, prostaglandins and oxytocin seem to act in synergy, perhaps along with endothelin-1, to trigger contractility through an increase in intracellular Ca2+ concentration. An overall view of these phenomena in which myometrial cells are the common targets of uterorelaxant and uterotonic agents appears essential for a rational use of tocolytic therapies and labour inductors.
 ...
PMID:Myometrial maturation and labour. 1181 51

An examination of cellular processes involved in myometrial function has been greatly assisted by the use of human myometrial cells in primary culture. However, these cells can be used only for several passages before they senesce, and responses to various agents change with time in culture. The use of transformed cells is limited, as they can be polynucleated and can lose or gain chromosomes. We have developed three telomerase-immortalized cell lines from term-pregnant human myometrium to eliminate variability between passage numbers and allow genetic manipulations of myometrial cells to fully characterize signal pathways. These cells have a normal karyotype and were verified to be uterine smooth muscle by immunocytochemical staining for smooth muscle cell-specific alpha-actin and high affinity oxytocin antagonist binding sites. The three cell lines and the cells in primary culture from which they were derived were examined by cDNA microarray analysis. Of >10 000 expressed genes, there were consistent changes in the expression of approximately 1% in the three immortalized cell lines. We were unable to detect any significant differences between primary and immortalized cells in signal pathways such as epidermal growth factor-stimulated epidermal growth factor receptor phosphorylation, insulin-stimulated Akt phosphorylation, oxytocin and lysophosphatidic acid-stimulated extracellular signal-regulated kinase 1 and 2 phosphorylation, myosin light chain phosphorylation, and interleukin-1 induction of IkappaBalpha degradation. The immortalized cells should be useful for a range of studies, including high throughput analyses of the effects of environmental agents on the human myometrium.
 ...
PMID:Immortalization and characterization of human myometrial cells from term-pregnant patients using a telomerase expression vector. 1524 28


<< Previous 1 2 3 Next >>