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

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the ability of the uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin may play a critical role in determining when endogenous secretion of PGF2 alpha begins. The cellular mechanisms that regulate uterine secretion of PGF2 alpha in response to oxytocin have not been completely defined. Several intracellular components that may contribute to this regulation have been studied, including phospholipase C (PLC), prostaglandin H endoperoxide synthase (PGS) and receptors for oxytocin. All of these components change during the oestrous cycle and are associated with the development of uterine secretory responsiveness to oxytocin. Progesterone appears to play the principal role in regulating oxytocin receptors, PLC and PGS. The conceptus appears to suppress the increase in receptors for oxytocin and PLC activity that typically occurs around the time of luteal regression.
...
PMID:Uterine secretion of prostaglandin F2 alpha in the ewe: regulation at the cellular level by ovarian hormones and the conceptus. 143 63

Progesterone and estradiol interact to regulate secretion of prostaglandin (PG) F2 alpha from the ovine endometrium in response to oxytocin. Two experiments were conducted to determine if these effects were due to changes in activity of phospholipase C or in the second messenger responsive pathways that regulate production of PGF2 alpha. In both experiments, ovariectomized ewes were assigned to one of four treatment groups (control, estradiol, progesterone, progesterone and estradiol). Steroids were administered, in vivo, to mimic the changes that occur during the estrous cycle. On Day 16 of steroid treatment, endometrial tissue was collected and incubated, in vitro, to measure activity of phospholipase C and release of PGF2 alpha. Treatment with progesterone, in vivo, enhanced basal and oxytocin-induced activity of phospholipase C and release of PGF2 alpha, in vitro. Estradiol suppressed oxytocin-induced activity of phospholipase C, both in the presence and absence of progesterone. In contrast to its effects on phospholipase C, estradiol inhibited basal and oxytocin-induced release of PGF2 alpha when administered alone, but not when administered with progesterone. Steroids had similar effects on the release of PGF2 alpha induced by phorbol 12-myristate 13-acetate and A23187. It was concluded that progesterone and estradiol regulate endometrial release of PGF2 alpha by affecting both the activity of phospholipase C and its associated second messenger responsive pathways that may regulate production of PGF2 alpha.
...
PMID:Activity of phospholipase C and release of prostaglandin F2 alpha by endometrial tissue from ovariectomized ewes receiving progesterone and estradiol. 201 59

The present studies were conducted to determine the effects of gonadotropins (LH and hCG) and prostaglandin F2a (PGF2a) on the production of "second messengers" and progesterone synthesis in purified preparations of bovine small luteal cells. Corpora lutea were removed from heifers during the luteal phase of the normal estrous cycle. Small luteal cells were isolated by unit-gravity sedimentation and were 95-99% pure. LH provoked rapid and sustained increases in the levels of [3H]inositol mono-, bis-, and trisphosphates (IP, IP2, IP3, respectively), cAMP and progesterone in small luteal cells. LiCl (10 mM) enhanced inositol phosphate accumulation in response to LH but had no effect on LH-stimulated cAMP or progesterone accumulation. Time course studies revealed that LH-induced increases in IP3 and cAMP occurred simultaneously and preceded the increases in progesterone secretion. Similar dose-response relationships were observed for inositol phosphate and cAMP accumulation with maximal increases observed with 1-10 micrograms/ml of LH. Progesterone accumulation was maximal at 1-10 ng/ml of LH. LH (1 microgram/ml) and hCG (20 IU/ml) provoked similar increases in inositol phosphate, cAMP and progesterone accumulation in small luteal cells. 8-Bromo-cAMP (2.5 mM) and forskolin (1 microM) increased progesterone synthesis but did not increase inositol phosphate accumulation in 30 min incubations. PGF2a (1 microM) was more effective than LH (1 microgram/ml) at stimulating increases in inositol phosphate accumulation (4.4-fold vs 2.2-fold increase for PGF2a and LH, respectively). The combined effects of LH and PGF2a on accumulation of inositol phosphates were slightly greater than the effects of PGF2a alone. In 30 min incubations, PGF2a had no effect on cAMP accumulation and provoked small increases in progesterone secretion. Additionally, PGF2a treatment had no significant effect on LH-induced cAMP or progesterone accumulation in 30 min incubations of small luteal cells. These findings provide the first evidence that gonadotropins stimulate the cAMP and IP3-diacylglycerol transmembrane signalling systems in bovine small luteal cells. PGF2a stimulated phospholipase C activity in small cells but did not reduce LH-stimulated cAMP or progesterone accumulation. These results also demonstrate that induction of functional luteolysis in vitro requires more than the activation of the phospholipase C-IP3/calcium and -diacylglycerol/protein kinase C transmembrane signalling system.
...
PMID:Second messenger systems and progesterone secretion in the small cells of the bovine corpus luteum: effects of gonadotropins and prostaglandin F2a. 254 70

The contractile response of the uterus is modified by sex steroids. In rabbit uterus, oestrogen promotes alpha-adrenergically-mediated contraction, whilst progesterone treatment results in beta-adrenergic relaxation. Examination of the mechanisms responsible for these changing adrenergic responses with sex steroids reveals multiple sites of regulation. Oestrogen increases alpha 1-receptor concentration and the linkage of the receptor to phospholipase C. In addition to this direct effect to promote contraction, oestrogen also uncouples the beta-receptor from adenylate cyclase. Progesterone, conversely, promotes relaxation through beta-receptors by uncoupling alpha 2-receptors from inhibition of adenylate cyclase. Thus sex steroids can regulate specific agonist responses at and beyond the receptor.
...
PMID:Hormonal regulation myometrial adrenergic responses: the receptor and beyond. 255 93

Prostaglandins are the products of cyclo-oxygenase and endoperoxide breakdown of free intracellular arachidonic acid (AA). Arachidonic acid is cleaved from membrane phospholipids by phospholipase A2 (PLA2) and phospholipase C (PLC). The human placenta is a rich source of lipocortin like PLA2 inhibitors. Human endometrium contains both PLA2 and PLC activity, and it is under research which pathway is predominant. Prostaglandin F2-alpha is derived from PLC endoperoxide, while prostaglandin E2 is formed by degradation of PG endoperoxide. Dated studies have found that prostaglandin F2-alpha was the predominant PG in the endometrium, whereas concentrations of PGE2 did not change during the cycle. In women estradiol stimulates PG synthesis from glands, and it has a role in mediating intracellular calcium in the human. Progesterone reduces the release of PGs from endometrial explants maintained in culture, while anti-progestins RU486 and ZK98734 stimulate the release of PGs from glandular cells of decidua. There seems to be a direct effect of progesterone on expression of PG synthetase, on the expression of a PG synthesis inhibitory protein, or an effect on a PLA2 activating protein. ZK98734 does not alter the metabolism of PGF2-alpha in the absence of added AA. Calmodulin also plays a role in regulating PG synthesis. Verapamil suppresses basal release of PGF2-alpha and prevents the rise in PG release caused by ZK98734. Progesterone suppresses PG synthesis in human endometrium. Colony stimulating factor- 1 (CSF-1) stimulates Ishikawa cell proliferation, acts on the hemopoietic system, and promotes the release of cytokines like interleukin-2, tumor necrosis factor (TNF), and interferons. Transforming growth factor alpha (TGF-alpha) mediates wound healing by promoting epithelial proliferation and angiogenesis and repairs desquamated endometrium. Epidermal growth factor (EGF) is present in the luminal surface of epithelial cells and myometrium but not in stromal cells. EGF p[lays a role in the proliferation of human endometrium and steroids modify this effect. INsulin-like growth factor (IGF-1) potentiates the activities of other mitogens like EGF. Basic fibroblast growth factor (bFGF) and acidic FGF (aFGF) have been detected in the uterine flushings and tissue of the guinea pig. FGF is a mediator of angiogenesis. different PGs affect vascular contractility, hemostasis, and myometrial contractility. PG synthesis is linked to menstrual dysfunction. The functions of growth factors and PGs may be related reflecting the autocrine and paracrine regulation of endometrial cell proliferation, a topic still under study.
...
PMID:Prostaglandins and growth factors in the endometrium. 269 20

Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of [3H]-arachidonic acid from stimulated, perfused, endometrial cells. The effect is independent of the mechanism of stimulation. Cortisol (10(-5)M but not 10(-7)M) has a similar effect in this system but estradiol (10(-7)M) is without effect. There was a positive correlation (p less than 0.05) between the magnitude of inhibition by progesterone and the day of cycle. The inhibitory action of progesterone on the release of arachidonic acid was greater in endometrial cells than in decidual cells and was apparent after fifteen minutes. The activities of commercial and endometrial cell-free preparations of phospholipase A2 and phospholipase C were unaffected by the presence of progesterone. We conclude that progesterone modulates release of [3H]-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity.
...
PMID:The effect of progesterone on the release of arachidonic acid from human endometrial cells stimulated by histamine. 308 83

Phospholipase C and 1,2-diacylglycerol lipase activities were demonstrated in human endometrium using 1-stearoyl-2-[1-14C]arachidonyl phosphatidylinositol as substrate. Phosphatidylinositol is hydrolysed by phospholipase C to inositol phosphates and to 1,2-diacylglycerol which is then further metabolized by 1,2-diacylglycerol lipase to release free arachidonic acid. In the present study the radiolabelled products formed (1,2-diacylglycerol and arachidonic acid) were measured following chloroform/methanol extraction and thin-layer chromatography. Phospholipase C activity was calcium dependent and optimal at pH 5.0-5.5 and 7.5; 1,2-diacylglycerol lipase activity was also calcium dependent, with an optimum pH of 5.5. A significant increase in 1,2-diacylglycerol production was stimulated by steroid sulphates. Pregnenolone sulphate, oestrone sulphate, testosterone sulphate and dehydroepiandrosterone sulphate stimulated 4, 3.2-, 1.8- and 2.6-fold increases in release respectively. Oestradiol sulphate stimulated a 25% increase in diacylglycerol release which was not significantly different from the control value. Progesterone stimulated a fourfold increase but other free steroids had no effect. Arachidonic acid release was increased in the presence of oestradiol sulphate, oestrone and oestradiol but reduced by oestrone sulphate, dehydroepiandrosterone sulphate, progesterone, dehydroepiandrosterone and, to a lesser extent, by pregnenolone sulphate and testosterone sulphate. 5-Androstene-3 beta,17 beta-diol had no effect on the liberation of either product. This study demonstrates a potential route for the liberation of arachidonic acid from phosphatidylinositol in human endometrium. The opposing effects of steroids on phospholipase C and 1,2-diacylglycerol lipase activity could be important in regulating the release of arachidonic acid by this pathway.
...
PMID:Hydrolysis of phosphatidylinositol by human endometrium: modulating effects of steroids on arachidonic acid and 1,2-diacylglycerol release. 337 59

Sodium butyrate (SB), a naturally occurring short-chain fatty acid, was investigated for its therapeutic value as an antiproliferative agent for vascular smooth muscle cells (SMCs). At 5-mmol/L concentration, SB had no significant effect on rat SMC proliferation. However, at the same concentration, SB inhibited platelet-derived growth factor (PDGF)-AA-, -AB-, and -BB-induced proliferation of SMCs. Exposure of SMCs to PDGF-BB resulted in activation of receptor intrinsic tyrosine kinase activity and autophosphorylation of beta-PDGF-receptor (beta-PDGFR). The activated beta-PDGFR physically associated and phosphorylated signaling molecules such as ras-GTPase activating protein (GAP) and phospholipase C gamma (PLC gamma). SB, in the absence of PDGF-BB, caused neither beta-PDGFR tyrosine phosphorylation nor phosphorylation and association of GAP and PLC gamma with beta-PDGFR. PDGF-BB-enhanced activation of receptor intrinsic tyrosine kinase activity and autophosphorylation of tyrosine residues of beta-PDGFR were unaffected by SB irrespective of whether SMCs were preincubated with SB before exposure to PDGF-BB plus SB or incubated concomitantly with PDGF-BB plus SB. Likewise, phosphorylation and association of GAP and PLC gamma with PDGF-BB-activated beta-PDGFR were unaffected. In addition, SB did not block PDGF-BB-stimulated, PLC gamma-mediated production of inositol triphosphate. Similarly, PDGF-BB-induced beta-PDGFR degradation was unaffected when SMCs were exposed to PDGF-BB plus SB, and SB by itself had no influence on beta-PDGFR degradation. Unlike beta-PDGFR kinase activity, mitogen-activated protein kinase (MAP-kinase) activity was stimulated by SB by about 2.7-fold. Exposure of SMCs to PDGF-BB caused an approximately 11.4-fold increase in MAP-kinase activity and this increase in activity was not significantly affected when cells were coincubated with PDGF-BB and SB (10.3-fold). However, pretreatment of SMCs with SB for 30 minutes and subsequent incubation in PDGF-BB plus SB abolished most of the PDGF-BB-induced MAP-kinase activity (4.6-fold). Transcription of growth response genes such as c-fos, c-jun, and c-myc were induced by PDGF-BB, and their induction was suppressed, particularly c-myc, by incubating SMCs with PDGF-BB plus SB. Similarly, preincubation of cells with SB for 30 minutes and subsequent incubation in PDGF-BB plus SB diminished PDGF-BB-induced transcription of c-fos, c-jun, and c-myc. However, SB by itself had no significant effect on c-fos, c-jun, and c-myc transcription.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Sodium butyrate inhibits platelet-derived growth factor-induced proliferation of vascular smooth muscle cells. 748 53

The possibility that progesterone or estradiol may regulate expression of G protein in the rat myometrium during the course of pregnancy has been investigated using 1) immunoblot analysis of Gi2 alpha, Gi3 alpha, and Gq alpha subunits and 2) hybridization blot analysis of subunit mRNA. Eighteen hours after administration, estradiol had significantly increased the levels of both Gi2 alpha subunit and Gi2 alpha mRNA (by 40% and 32%, respectively). In control pregnant rats, we observed similar changes at the end of pregnancy, when myometrial concentrations of estradiol had increased, i.e., a 41% increase in immunoreactive Gi2 alpha subunit that correlated with a parallel 45% increase in mRNA levels. In contrast, levels of immunoreactive Gi3 alpha subunit and mRNA, which decreased with advancing gestation, were not influenced by estradiol or progesterone administration. Progesterone administration resulted 30 h later in a significantly decreased level of Gq alpha immunoreactivity (32%) and Gq alpha mRNA (30%). In control rats, Gq alpha protein and mRNA were also significantly lower at midpregnancy under progesterone dominance vs. term. At this stage, a twofold increase in Gq alpha subunit correlated with a 40% increase in mRNA levels. These results demonstrate that myometrial Gi2 alpha and Gq alpha subunits are physiological targets for estradiol and progesterone, respectively, in vivo. Alterations of these G protein levels are discussed in relation to their mediating effects on adenylyl cyclase activity or the phospholipase C pathway during the course of pregnancy.
...
PMID:Regulation of myometrial Gi2, Gi3, and Gq expression during pregnancy. Effects of progesterone and estradiol. 766 57

The effects of progesterone and GTP gamma S on phospholipid N-methylation and sphingomyelin synthesis were studied in plasma-vitelline membranes isolated from amphibian (Rana pipiens) oocytes. Plasma-vitelline membranes were preincubated with S-adenosyl-L-[methyl-3H]methionine for 2 min at 20 degrees C and total phospholipids extracted at 0, 15, 30 and 60 s after addition of progesterone and/or GTP gamma S. Progesterone levels (3 microM) that induce meiosis in the intact oocyte stimulated [3H-methyl]incorporation into phosphatidylmonomethylethanolamine (PME) 9-10-fold over the first 60 s, with smaller increases in phosphatidyldimethylethanolamine (PDE) and phosphatidylcholine (PC). [methyl-3H] labeling of sphingomyelin (SM) rises after 30 s, approaching that of [methyl-3H]PME by 60 s. 17 beta-Estradiol, a noninducer of meiosis, was inactive. When oocytes were prelabeled with [3H]palmitic acid, it was found that a fall in [3H]ceramide coincides with the transient increase in [3H]SM, indicating that the end product of N-methylation (PC) undergoes a transfer reaction with ceramide to form SM and 1,2-DG. GTP gamma S levels previously reported to stimulate PC-specific phospholipase C activity in oocyte plasma membranes (5 microM) also stimulated both [methyl-3H]PME and [methyl-3H]SM formation. An inhibitor of phospholipid N-methylation, 2-(methyl-amino)ethanol, blocked stimulation of [methyl-3H]SM synthesis by both progesterone and GTP gamma S as well as induction of meiosis by progesterone. Progesterone thus acts at the oocyte plasma membrane to stimulate PE N-methyltransferase and SM synthase. The finding that GTP gamma S mimics progesterone suggests that N-methyltransferase is mediated by G-protein(s). The transient increase in 1,2-DG which we had previously reported to occur within 1-2 min following progesterone stimulation of the Rana oocyte appears to arise from PC by two different pathways: SM synthesis and hydrolysis of PC by phospholipase C.
...
PMID:Progesterone-induced phospholipid N-methylation and sphingomyelin synthesis in the amphibian oocyte plasma membrane: a second source of the 1,2-diacylglycerol second messenger associated with the G2/M transition. 780 20


1 2 3 4 5 6 7 Next >>

---