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)

1. The characteristics of vasopressin-stimulated phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) and phosphatidylcholine (PtdCh) hydrolysis were examined in A10 vascular smooth muscle cells (VSMC), by assessing the formation of [3H]-inositol phosphates ([3H]-IP) and the accumulation of the phospholipase D (PLD) specific product, [3H]-phosphatidylbutanol ([3H]-PtdBuOH). 2. Vasopressin ([Arg8]-VP) and a number of related analogues stimulated the accumulation of [3H]-IP and [3H]-PtdBuOH with similar EC50 values, generating the same rank order of potency for each response (Arg8-VP = vasotocin = Lys8-VP much greater than oxytocin). 3. Inhibition of vasopressin-stimulated [3H]-IP and [3H]-PtdBuOH accumulation by the V1a receptor antagonists, Des-Gly9[beta-mercapto-beta,beta,-cyclopentamethylene propionyl, O-Et-Tyr2,Val4,Arg8]-vasopressin generated similar IC50 values suggesting that both these responses are mediated through the activation of a single V1a receptor subtype. 4. The onset of vasopressin-stimulated inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) mass formation preceded [3H]-PtdBuOH accumulation indicating that PtdCh hydrolysis was activated subsequent to PtdIns(4,5)P2 breakdown. 5. The protein kinase C (PKC) activator, tetradecanoylphorbol acetate (TPA) also stimulated [3H]-PtdBuOH accumulation. Preincubation with the PKC inhibitor Ro-31-8220 abolished both TPA- and vasopressin-stimulated [3H]-PtdBuOH, suggesting that the intermediate activation of protein kinase C is involved in the regulation of PLD by vasopressin. 6. Pretreatment of the A10 VSMC with Ro-31-8220 (100 microM) also potentiated vasopressin-stimulated Ins(1,4,5)P3 mass formation.Therefore stimulation of PKC may have opposing roles in the regulation of agonist activation of PLC and PLD.7. Preincubation of the cells with EGTA, verapamil, or the receptor-operated calcium channel antagonist, SK&F 96365, reduced vasopressin-stimulated [3H]-PtdBuOH accumulation by approximately 30%, suggesting that influx of calcium has a significant role to play in the regulation of vasopressinstimulated PLD activity.
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PMID:Vasopressin-stimulated [3H]-inositol phosphate and [3H]-phosphatidylbutanol accumulation in A10 vascular smooth muscle cells. 133 Jan 54

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.
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PMID:Phospholipase D activity of human amnion cells stimulated with phorbol ester and bradykinin. 850 57

The regulation of phospholipase D (PLD) activity in the human amniotic membrane was examined using primary cultures of amnion cells. Cultured amnion cells were labelled with [3H]oleic acid, and PLD activity was determined as the amount of [3H]phosphatidylethanol (PEt) produced during incubation in the presence of 0.1% ethanol. PLD activity in cultured amnion cells was activated by addition of arginine vasopressin and oxytocin. PLD activity was also stimulated by treatment was arachidonic acid, the product of phospholipase A2 (PLA2), and phospholipase C (PLC). These results indicate that PLD in amnion cells is activated by substances present in amniotic fluid, and that cross-talk between phospholipases A2, C and D may occur in amnion cells.
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PMID:Activation of phospholipase D in cultured human amnion cells. 874 70

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

Intracellular mediators regulating the initiation of parturition are not fully understood. This study was designed to determine the possible mechanism of oxytocin-induced uterine contractility during labour. In-vitro isometric contraction studies were performed with longitudinal strips of human pregnant myometrium in the presence and absence of the protein kinase C inhibitors, staurosporine and RO 31-8220, and the tyrosine kinase inhibitor, genistein. Phospholipase D activity was measured by employing the transphosphatidylation reaction. Staurosporine significantly reduced oxytocin-stimulated contractile activity with mean activity reduced by > 50% following the addition of 10(-6) M staurosporine (P < 0.01), while addition of 10(-5) M resulted in a measured mean contractile activity of approximately 10% of the control (P < 0.001, n = 5). Similarly, uterine activity was minimal with oxytocin application following incubation with RO 31-8220, mean contractile activity being reduced by approximately 40% by the addition of 10(-7) M RO 31-8220 (P < 0.05) and by approximately 87% by the addition of either 10(-6) or 10(-5) M (P < 0.01, n = 3). Conversely, addition of genistein (10(-7) and 10(-6) M) had little effect on oxytocin-induced contractions, although at a higher concentration (10(-5) M) a significant reduction in oxytocin-induced contractile activity was observed (P < 0.01). Oxytocin evoked phospholipase D activation in a concentration- and time-dependent manner in cultured human pregnant myometrial cells (n = 4). These results indicate that activation of protein kinase C and tyrosine kinase are involved in the regulation of oxytocin-mediated myometrial contractile activity and that a coupled phospholipase D/phosphatidate phosphohydrolase pathway may play a role in the sustained stimulation of myometrial activity during labour.
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PMID:Activation of protein kinase C is required for oxytocin-induced contractility in human pregnant myometrium. 894 42

Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer apoptosis remain unclear. To investigate the underlying genes and networks regulated by FOXP3 in breast cancer, RNA sequencing was performed to compare FOXP3-overexpressing MDA-MB-231 cells and control MDA-MB-231 cells. Differentially expressed genes were identified, and functional enrichment analysis comparing the two groups was performed. The differentially expressed genes were mainly enriched in phagosomes, oxytocin, serotonergic synapses and the phospholipase D signaling pathway. Furthermore, gene set enrichment analysis revealed the enrichment of a gene signature associated with apoptosis in FOXP3-overexpressing MDA-MB-231 cells compared with wild-type cells. Further analysis showed that programmed cell death 4 (PDCD4), a key molecule involved in apoptosis, was overexpressed in FOXP3-MDA-MB-231 cells. Reverse transcription-quantitative PCR and western blotting showed that FOXP3 upregulated the expression of PDCD4 in breast cancer cells. Clinical sample analysis using a public database showed that the expression level of PDCD4 was associated with breast cancer clinical stages. Overall, the present study suggested that FOXP3 can promote the apoptosis of breast cancer cells by upregulating the expression of PDCD4, thus exerting a tumor suppressive function.
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PMID:Forkhead box P3 promotes breast cancer cell apoptosis by regulating programmed cell death 4 expression. 3310 86