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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet activating factor (PAF) stimulated production of prostaglandin (PG) I2, PGE2, and PGF2 alpha by rat liver cells (the C-9 cell line); as little as 0.2 nM PAF was effective. Enantio-PAF was 1000-fold less effective. Lyso-PAF, at levels ranging from 0.1 to 1.0 microM, did not stimulate PGI2 production. The synthesis of PGI2 was essentially complete in 10 min. The stimulation by PAF of PGI2 production was inhibited by the PAF antagonists L-659,989, kadsurenone, L-652,731, and BN 52021; the values for 50% inhibition (IC50) were 0.02, 0.19, 0.21, and 0.73 microM, respectively. The antagonists L-659,989 and BN 52021 had no effect on the levels of 6-keto-PGF1 alpha stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), palytoxin, melittin, the Ca2+ ionophore-A-23187, colchicine, transforming growth factor alpha, or exogenous arachidonic acid. The effect of PAF on arachidonic acid metabolism was inhibited by prior exposure of the cells to PAF. Prior treatment of the rat liver cells at 37 degrees with the TPA-type tumor promoters TPA, teleocidin, and aplysiatoxin, as well as with the second stage tumor promoter mezerein, all of which activate the Ca2+/phospholipid-dependent protein kinase (protein kinase C), resulted not only in homologous desensitization to the TPA-type tumor promoters and mezerein, but also in heterologous desensitization to PAF. Stimulation of PGI2 production by palytoxin, the Ca2+ ionophore A-23187, or exogenous arachidonic acid was not inhibited by such prior treatments with the TPA-type tumor promoters. Prior treatment of the cells at 37 degrees for 30 min with the non-TPA-type tumor promoters okadaic acid or palytoxin, both of which do not activate protein kinase C, did not result in heterologous desensitization to PAF.
Mol Pharmacol 1988 Dec
PMID:Platelet-activating factor stimulates arachidonic acid metabolism in rat liver cells (C-9 cell line) by a receptor-mediated mechanism. 284 46

Cultured human endometrial stromal cells were found to release placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Progesterone had no effect on PP5 release, but cholera toxin and 12-O-tetradecanoylphorbol 13-acetate stimulated PP5 release in a time- and concentration-dependent fashion. Prostaglandin E2 (PGE2) caused a parallel increase in cAMP and PP5 release in a time- and concentration-dependent fashion. The lowest PGE2 concentration which increased cAMP and PP5 release was 1 X 10(-9) M. Maximal increase in cAMP (42-fold) and PP5 (25-fold) release was obtained by 10(-5) M PGE2. Stimulation of cAMP by PGE2 was detectable at 15 min and was followed by an increased PP5 release at 24 h. The concentrations of prostaglandin F2 alpha (PGF2 alpha) which stimulated cAMP and PP5 release were pharmacological suggesting that this effect is nonspecific. The results indicate that the activation of cAMP- and protein kinase C-dependent pathways in endometrial stromal cells increases the production of PP5. PGE2 could be one of the physiological ligands employing the cAMP-dependent pathway in endometrial stromal cells.
Mol Cell Endocrinol 1988 Dec
PMID:Regulation of the production of placental protein 5 by human endometrial stromal cells; the role of prostaglandins E2 and F2 alpha. 285 Sep 54

We reported recently the presence of somatostatin-like immunoreactivity (SLI) in the glomerulus of rat kidney. In the present study, we examined factors affecting SLI release from isolated rat glomeruli using a perifusion system. Perifusate containing a mixture of essential amino acids stimulated SLI release, while other hormonal agents such as parathyroid hormone, vasopressin, angiotensin II, bradykinin, epinephrine, PGE2, known to have direct actions on the glomerulus, had no discernible effect on SLI release. Addition of somatostatin to the perifusate did not affect either basal or angiotensin II-stimulated PGE2 release from isolated glomeruli. Our preliminary results demonstrate the stimulatory effect of mixed amino acids on somatostatin release from isolated glomeruli. Further studies are needed to elucidate the possible physiological significance of the present findings.
Mol Cell Endocrinol 1985 Jul
PMID:Amino acids release somatostatin-like immunoreactivity from isolated rat glomeruli. 286 84

Addition of zymosan (20 particles/cell) to suspensions of resident rat peritoneal macrophages caused an increase in the concns of prostaglandins and cyclic AMP. Preincubation of the cells with inhibitors of arachidonate metabolism led to inhibition of prostaglandin, but not of cyclic AMP, formation, which suggested that the two processes may occur independently of each other in phagocytosing cells. The luminol-dependent chemiluminescence associated with the addition of zymosan to the cells consisted of a minor, Ca2+-dependent, glucose-independent component and a major, glucose-dependent, Ca2+-independent component. Only the minor, Ca2+-dependent component appeared to be related to the lipoxygenation of arachidonic acid. Close examination of the production of prostaglandins and cyclic AMP and of chemiluminescence after zymosan addition, indicated that the expanded pool of endogenous cyclic AMP was probably not a negative modulator of the other two processes, although they remained susceptible to inhibition by exogenously-added cyclic AMP analogues or PGE2. The events induced by zymosan may be relevant to the physiological roles of prostaglandins during the inflammatory response.
Mol Immunol 1985 Dec
PMID:Reactive-oxygen formation and its relationship to prostaglandin and cyclic AMP production by zymosan-treated rat peritoneal macrophages. 300 75

Incubation of isolated rat adipocytes with 1 microM arachidonic acid (20:4) coupled to equimolar amounts of bovine serum albumin (BSA) results in the cellular uptake of the fatty acid and a subsequent inhibition of insulin-stimulated antilipolysis and lipogenesis without altering glucose transport. These effects are apparently not mediated at the insulin receptor level since insulin binding is not altered in arachidonate-enriched fat cells. In addition, effects on antilipolytic and lipogenic are not specific for arachidonic acid. Oleic or palmitic acid can mimic these effects in both insulin-stimulated and PGE2-stimulated cells. Adipocyte enrichment with 20:4, however, specifically inhibits the insulin-stimulated turnover of phosphoinositides. The latter can be specifically prevented by preincubation with ibuprofen. These results suggest that the level of intracellular arachidonate may play a major role in modulating insulin-stimulated phosphoinositide turnover and thereby indirectly regulate certain aspects of insulin action which involve lipid metabolism.
Mol Cell Endocrinol 1986 May
PMID:Arachidonic acid inhibition of insulin action and phosphoinositide turnover in fat cells. 301 56

[14C]Estradiol, [14C]estrone, [14C]progesterone and [3H]prostaglandins (PGs) E2 and F2 alpha, when incubated with myometrial plasma membranes (MPM) at a concentration of 1 X 10(-6) M for 1 h at 37 degrees C, bind into MPM at pmolar concentrations. Unlabeled steroids inhibited [3H]PGE2 and [3H]PGF2 alpha binding to MPM in a dose-dependent manner. Membrane-bound and free steroids or PGs were found to be essentially unchanged under the present incubation conditions. Ca2+ ions up to 10 mM increased steroid binding into MPM. Molecular interactions between steroids and MPM were assessed by measuring the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), and by estimating the changes in the allosteric properties of MPM-bound (Na+ + K+)ATPase by fluoride (F-). Steroids appear to increase the MPM fluidity, evaluated through changes in the Hill coefficient for MPM-bound (Na+ + K+)ATPase by F- and by the fluorescence polarization method. Binding of sex steroids to MPM increased the membrane fluidity and decreased the binding of the uterus stimulatory PGs by membrane receptors. These studies provide a basis for postulating that a 'non-genomic' mechanism of sex steroids induces reduction of uterine contractions.
Mol Cell Endocrinol 1986 May
PMID:Sex steroid and prostaglandin interactions upon the purified rat myometrial plasma membranes. 301 59

The regulation of cAMP generation in rat myometrium during gestation was investigated comparatively to the stimulations evoked in the estrogen-dominated myometrium. At the onset of gestation, there was a progressive attenuation in both tissue cAMP accumulation and adenylate cyclase activation in response to isoproterenol and prostaglandins (PGs) (PGE2 and prostacyclin, PGI2), as well as to cholera toxin and to forskolin. Minimal responses were observed at midgestation (day 12). The decline in isoproterenol-mediated cAMP accumulation could not be ascribed to alterations in either beta-adrenergic receptor density or coupling properties. Treatment of day 12 myometrium with islet-activating protein (IAP), pertussis toxin, caused a reversal of the attenuated beta-adrenergic--as well as cholera toxin--responses, suggesting that the inhibitory regulatory protein, Gi, was involved. However IAP treatment did not improve the PGE2-mediated stimulatory effect. In membranes from day 12 myometrium, the amount of [32P]NAD incorporated by IAP into the Mr = 41,000 peptides (alpha i, subunit of Gi was markedly increased compared to membranes from day 0 tissue. There was also a consistent decrease (25%) of the label incorporated by cholera toxin into the Mr = 52,000 (major) and 45,000/53,000 (minor) peptides (alpha s, subunit of Gs). The advanced stages of gestation were associated with a progressive restoration of cAMP responses to isoproterenol, cholera toxin, and forskolin with a full responsiveness before parturition (day 22). By contrast, the inability of PGE2 to generate any active Gs (stimulatory regulatory protein)-C complex persisted and coincided with the development of PGE2-induced inhibition of cAMP generation due to isoproterenol. The inhibitory effect, which was similarly evoked by PGE2 as well as by PGI2 and PGF2 alpha, was prevented by IAP. The data suggest that alterations of the stimulatory Gs-mediated pathway, which culminated at midgestation, is due at least in part to an increase in the abundance of Gi relative to Gs. Additional alterations operate at the level of the prostaglandin receptor(s) with a conversion from a stimulatory (Gs-mediated) cAMP response in the estrogen-dominated myometrium to an inhibitory (Gi-mediated) effect, fully expressed in the final stage of gestation.
Mol Pharmacol 1987 Aug
PMID:Heterologous regulations of cAMP responses in pregnant rat myometrium. Evolution from a stimulatory to an inhibitory prostaglandin E2 and prostacyclin effect. 303 39

The purpose of this study was to establish whether the nephron segments recognized as PGE2 target sites in the rabbit, i.e. the proximal tubule, the thick ascending limb and the collecting tubule, are also sites of PGE2 production. We therefore developed a microimmunoassay sensitive enough to allow the measurement of PGE2 on microdissected tubular segments about 1 mm in length. Under the conditions used (30 min incubation at 20 degrees C), a basal rate of PGE2 production was measured in the cortical (CCT) and medullary portions of the collecting tubule, as could be expected. In the presence of 10(-4) M sodium arachidonate, it was shown that: (1) The thin descending limb (TDL) is also an active site of PGE2 formation. When expressed per mm tubule length the amounts formed were lower in TDL than in CCT (14.1 +/- 2.7 SE pg/mm, n = 5, vs. 93.5 +/- 10.7, n = 8). They were quite comparable, however, when expressed per microgram total proteins (0.70 ng in TDL vs 0.6 in CCT). (2) A slight PGE2 production was noted in the connecting tubule but it was likely due to contamination by adjacent CCT cells. (3) In the other nephron segments, only negligible amounts of PGE2 were formed, which are probably of no physiological significance.
Mol Cell Endocrinol 1986 Apr
PMID:Sites of prostaglandin E2 (PGE2) synthesis along the rabbit nephron. 308 17

Rat renal mesangial cells possess morphological and functional features of smooth muscle cells in culture, such as intracellular myosin filaments, A II receptors and a contractile response to A II. Furthermore, they represent the main glomerular site of PGE2 synthesis. In the presence of A II (50 nM), their PGE2 production rate was significantly increased, this effect being potentiated by arachidonic acid (3 micrograms/ml). After a prior inhibition of arachidonic acid metabolism by cyclooxygenase inhibitors (indomethacin 1 microM or naproxen 0.02 microM) or by a cyclo- and lipoxygenase inhibitor (phenidone 670 microM), the percentage of cells contracting in response to various A II concentrations (10 pM to 10 nM) was significantly enhanced as compared to the basal conditions. On the contrary, the percentage of cells presenting a contractile response to A II in the presence of exogenous PGE2 (50 ng/ml) or of arachidonic acid (3 micrograms/ml) was significantly decreased. These modifications were not related to some changes in the A II receptor properties of the cells, i.e. the number of receptor sites and their affinity constant. The data demonstrate that the contractile response of glomerular mesangial cells is modulated by the PGE2 content of their incubation medium. Since their own PGE2 production rate is enhanced in the presence of A II, this cellular response may represent a local regulatory mechanism of their contractile properties.
Mol Cell Endocrinol 1986 Sep
PMID:Glomerular mesangial cell contractility in vitro is controlled by an angiotensin-prostaglandin balance. 309 26

We have investigated the involvement of arachidonic acid release and metabolism in the mitogenic response, i.e., [3H]thymidine incorporation, to epidermal growth factor (EGF) in BALB/c 3T3 cells. EGF induces release of arachidonate and prostaglandin (PG) formation after its addition to BALB/c 3T3 cells at the same concentrations that stimulate mitogenesis. Further, EGF-stimulated mitogenesis is blocked by inhibitors of arachidonate metabolism including indomethacin, eicosatetraynoic acid, and dexamethasone, whereas the addition of major arachidonate products in BALB/c 3T3 cells, PGE2, PGF2 alpha, and their intermediates PGG2 and PGH2, stimulate mitogenesis in synergism with EGF. The addition of PGs to BALB/c 3T3 cells also overcame indomethacin- and eicosatetraynoic acid-inhibited responses to EGF. Indomethacin must be added with EGF in order to block arachidonate metabolism and subsequent mitogenesis. These results suggest that the release of arachidonic acid and its subsequent metabolism is an apparent early requirement for the initiation of cell cycle traversal by EGF.
Mol Pharmacol 1988 Jun
PMID:Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor. 313 9


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