Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) induce platelet aggregation and are potent vasoconstrictors, and they have been implicated in coronary vasospasm and myocardial infarction. The TXA2 mimetic [1S-(1 alpha, 2 beta (5Z), 3 alpha (1E,3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-h eptenoic acid (IBOP) was used to characterize binding to microsomal membrane preparations from saline-perfused guinea pig atria (GPA) and ventricles (GPV). [125I]IBOP bound to GPA and GPV in a protein-dependent and saturable manner, although total binding was two-fold greater and non-specific binding was proportionately less in GPA compared to GPV. Analysis of equilibrium binding data indicated one class of binding sites in both GPA and GPV with Kd values of 333 +/- 117 and 645 +/- 187 pM, respectively, which were in close agreement with kinetically determined Kd values of 226 and 882 pM, respectively. Bmax values of GPA and GPV of 57 +/- 5.6 and 24 +/- 4.3 fmol/mg protein were significantly different (P < 0.01). Ki values (from IC50s) were determined for various TXA2/PGH2 analogues and prostaglandins in competition binding assays with [125I]IBOP. The rank order for ability to inhibit binding in GPA was U46619 = SQ29548 > I-PTA-OH > PGF2 alpha = PGE2. In GPV, the rank order was U46619 = SQ29548 > PGF2 alpha = I-PTA-OH = PGE2. [125I]IBOP binding to GPA and GPV was completely displaced by the TXA2/PGH2 agonist U46619 and by the TXA2/PGH2 antagonist SQ29548.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1994 Jul
PMID:Characterization of thromboxane A2/prostaglandin H2 binding sites in guinea pig cardiac membrane preparations. 796 60

Dietary deficiency of magnesium (Mg) in rodents results in cardiomyopathic lesion formation. In our rat model, these lesions develop after 3 weeks on the Mg-deficient diet; significant elevation of several cytokines, IL-1, IL-6 and TNF alpha also occurs. In probing the mechanisms of lesion formation, we obtained data supporting the participation of free radicals (Freedman AM et al.: Bioch Biophys Res Commun 1990; 170: 1102). Recently, we identified an early elevation of circulating substance P and proposed a role of neurogenic peptides during Mg-deficiency (Weglicki WB, Phillips TM: AM J Phys 1992;262:R734). The present study was designed to evaluate the contribution of neurogenic peptides to the pathogenesis of Mg-deficiency. In the blood, substance-P and calcitonin gene related peptide (CGRP) are elevated during the first week on the diet. During the second week, circulating histamine, PGE2 and TBAR-materials were elevated and red cell glutathione was reduced, all prior to the elevation of the inflammatory cytokines during the third week. When the rats were treated with the substance P-receptor blocker [CP-96,345], the levels of substance P and CGRP remained elevated; however, increases in histamine, PGE2, TBAR-materials, and the decrease in red cell glutathione were inhibited; also, the development of cardiac lesions was inhibited significantly. These data support a central role for neurogenic peptides, especially substance P, in the development of cardiomyopathic lesions during Mg-deficiency.
Mol Cell Biochem 1994 Jan 26
PMID:Neurogenic peptides and the cardiomyopathy of magnesium-deficiency: effects of substance P-receptor inhibition. 802 89

A cDNA that when expressed has the binding and functional characteristics of the pharmacologically defined EP2 prostaglandin (PG) receptor [Cardiovasc. Drug Rev. 11:165-179 (1993)] has been cloned from a human placenta library. This clone, known as Hup-4, encodes a protein of 358 amino acids that has only approximately 30% overall identity with other PG receptors, including mouse and human clones that have been designated as EP2 receptors [J. Biol. Chem. 268:7759-7762 (1993); Biochem. Biophys. Res. Commun. 197:263-270 (1993)]. In COS-7 cells transfected with Hup-4, PGE2 stimulated the formation of cAMP with an EC50 of approximately 50 nM. The EP2-selective agonists AH13205 and butaprost were also active, with EC50 values in the range of 2-6 microM. The order of potency of PGs for competition with binding of [3H]PGE2 to membranes prepared from COS-7 cells transfected with Hup-4 was PGE2 > or = PGE1 > 16,16-dimethyl-PGE2 > or = 11-deoxy-PGE1 > butaprost > AH13205 > 19(R)-OH-PGE2. Natural PGs and analogues that are selective for the FP (PGF2a), DP (PGD2), EP1 (sulprostone), EP3 (MB 28767), and EP4 (1-OH-PGE1) receptors were inactive or competed poorly with the binding of [3H]PGE2 (< 50% displacement of specific binding at 10 microM). Northern blot analysis showed the presence of a Hup-4 message of approximately 3.1 kilobases in mRNA from human lung and placenta. Reverse transcription-polymerase chain reaction studies also indicated that Hup-4 is probably expressed in human uterus and in HL-60 (human promyelocytic leukemia) cells. Our findings suggest that Hup-4 encodes the pharmacologically defined EP2 receptor, whereas the mouse and human cDNAs previously classified as EP2 may represent another EP receptor subtype or the recently defined EP4 subtype [Prostaglandins 47:151-168 (1994)].
Mol Pharmacol 1994 Aug
PMID:Cloning of a novel human prostaglandin receptor with characteristics of the pharmacologically defined EP2 subtype. 807 84

Inhaled furosemide protects asthmatic subjects against bronchial obstruction caused by indirect provocants. We have attempted to correlate the protective effect of furosemide with its ability to alter prostaglandin (PG) synthesis by the airway epithelium. Human epithelial cells from nasal polyps and bronchi were cultured in DME-Ham's F12 medium with 10% fetal calf serum. Confluent cells (days 6 through 8) were incubated for 30 min in fresh medium, and the PGs in the supernatant were measured by radioimmunoassay. Spontaneous output (ng.ml-1.mg-1 cell protein) was as follows (mean +/- SEM): PGE2 = 7.74 +/- 2.10 (n = 12), PGF2 alpha = 1.66 +/- 0.12 (n = 15), 6-keto-PGF1 alpha = 4.32 +/- 1.37 (n = 11), PGD2 = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE2 = 7.24 +/- 0.80 (n = 32), PGF2 alpha = 1.38 +/- 0.12 (n = 17), 6-keto-PGF1 alpha = 6.79 +/- 2.50 (n = 15), PGD2 = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid (25 micrograms/ml) for 30 min significantly increased the amounts of the four PGs. Incubation with furosemide (10(-4) M) for 30 min caused a marked reduction in both basal and arachidonic acid-stimulated production of PGE2 and PGF2 alpha but did not reduce production of 6-keto-PGF1 alpha and PGD2. Incubation with bumetanide (10(-4) M) for 30 min did not modify the PGE2 synthesis by nasal epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Apr
PMID:Effect of furosemide on prostaglandin synthesis by human nasal and bronchial epithelial cells in culture. 813 54

The effects of one of the main components of fish oil, docosahexaenoic acid (DHA), on prostaglandin (PG) and Ca2+ signaling pathways were examined in intact mucosa and freshly isolated crypt cells of rabbit descending colon. Preincubation of serosal mucosa for 20 min with 1 microM DHA fully suppressed the short-circuit and transepithelial conductance increase induced by serosal addition of 10 microM arachidonic acid (AA). DHA at 1 microM also prevented the Cl- secretion promoted by 10 microM AA, as estimated by unidirectional 36Cl flux measurements (net flux = 0.68 +/- 0.30 versus -1.91 +/- 0.20 microEq/hr/cm2, four experiments, p < 0.001), whereas it did not affect the electrophysiological and ion flux responses to PGE2. Addition of 1 microM DHA to the serosal side of the mucosa also inhibited the PG cascade activation elicited by AA (PG synthesis and second messenger cAMP increase). In vitro assays of colonic cyclooxygenase activity showed that 1 microM DHA inhibited (with a 20-min lag) cyclooxygenase activity to the same extent as 5 microM indomethacin (approximately 82% and 80%, respectively). DHA also affected the Ca2+ signaling pathway; in isolated crypt cells, the cytosolic free Ca2+ concentration ([Ca2+]i) dropped by 49 +/- 7.6% (mean +/- standard error, six experiments) after incubation with 1 microM DHA. The sustained phase of the [Ca2+]i response to 500 nM concentrations of the intracellular Ca(2+)-ATPase inhibitor thapsigargin was also inhibited within 150 sec upon 1 microM DHA addition (141 +/- 5.8 versus 243 +/- 8.2 nM [Ca2+]i mean +/- standard error, eight experiments, p < 0.01). The [Ca2+]i-lowering effect of DHA, which was not achieved by incubation with other free fatty acids, was not prevented by removal of Na+ from the incubation medium (-46 +/- 4.3% versus -47 +/- 3.8%, mean +/- standard error, four experiments), nor it was mediated by cAMP-, protein kinase C-, or calmodulin-dependent mechanisms. The incubation of highly purified basolateral membranes of crypt cells with 1 microM DHA for 1 min produced a 5-fold increase (IC50 = 0.25 microM) in the plasma membrane Ca(2+)-ATPase activity (34.3 +/- 2.73 versus 6.02 +/- 0.50 nmol/mg of protein/min, mean +/- standard error, four experiments, p < 0.0001), thus indicating that the DHA effects on the Ca2+ pathway were mediated mainly by an increase in plasma membrane Ca2+ pump activity. These findings suggest that DHA is a powerful modulator of the cellular response to activation of PG and Ca2+ signaling pathways.
Mol Pharmacol 1994 Apr
PMID:Docosahexaenoic acid and signaling pathways in rabbit colon. 818 54

We describe prostaglandin (PG) biosynthesis by microsomal-enriched preparations of fat body from larvae of the tobacco hornworm Manduca sexta. Four major PGs were synthesized under most experimental conditions, PGA2, PGE2, PGD2 and PGF2 alpha. PGA2, was the predominant product under most conditions. Unlike mammals, in which PGA2, is generally thought to arise from non-enzymatic rearrangements of PGE2, the fat body preparations did not convert exogenous PGE2 into PGA2. These findings suggest that PGA2 is an important fat body product that is synthesized by a route that does not involve PGE2. The PG synthase activity and the overall profile of PG synthesis were sensitive to experimental conditions, including incubation time, temperature, and protein concentration. Optimal PG biosynthesis was observed with 1 mg of microsomal-rich protein, incubated at 30 degrees C for 1-2 min. The fat body preparations is sensitive to two non-steroidal anti-inflammatory drugs, indomethacin and naproxen, both of which inhibited PG synthesis at low dosages.
Insect Biochem Mol Biol 1994 May
PMID:Prostaglandin biosynthesis by fat body from the tobacco hornworm, Manduca sexta. 820 44

The initiation of human parturition remains an enigma but is thought to involve a number of hormonal signals such as oxytocin and prostaglandins. One other possible signal is placentally derived corticotropin-releasing hormone (CRH). We have recently reported that the human myometrium expresses a specific receptor for CRH which changes to a high affinity state prior to term. In view of this we sought to determine whether this receptor is functionally linked to some of the known modulators of myometrial function. Myometrial membranes were prepared by differential centrifugation from either pregnant (caesarian section) or non-pregnant (hysterectomy) myometrium. For binding studies the membranes were incubated with radiolabelled oCRH at 22 degrees C for 2 h. For second messenger studies they were incubated at 37 degrees C for 10 or 30 min with either 0.5 mM ATP and 10 mM theophylline (cAMP) or 0.05 mM arachidonic acid or 0.5 mM linoleic acid (PGE2). When increasing concentrations of membranes were incubated with radiolabelled oCRH an interesting phenomenon was observed. In non-pregnant membranes the binding reached a plateau, whereas in membranes prepared from pregnant myometrium, the binding decreased at concentrations above 130 micrograms/ml. Possible explanations for this phenomenon include an inhibitor which prevents ligand-receptor binding or an enzyme which destroys the receptor binding region of the ligand. Incubation of both types of membranes with GTP or its analogue, GppNHp, resulted in a dose-dependent inhibition of specific binding suggesting that the myometrial CRH receptor is linked to a G regulatory protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Mar
PMID:The human myometrial CRH receptor: G proteins and second messengers. 820 32

The effect of a previous exposure to hyperbaric oxygen (HBO) on the synthesis capacity of prostaglandin (PG) and thromboxane (TX) was investigated in the brain of male rats. Three groups of rats were used: 1. Neurotoxic HBO (n = 11): The rats were exposed to sixfold the atmospheric pressure (101.3 kPa), i.e., 6 absolute atmospheres (ATA), of pure O2 up to the first convulsion (6 ATA O2); 2. Mild hyperoxia (n = 10): The rats were exposed to compressed air at the same absolute pressure and for a similar time than that of the neurotoxic HBO group (here PO2 is 1.26 ATA); 3. Normoxia at atmospheric pressure (PO2 is 0.21 ATA) for control. There was no convulsion in groups 2 and 3. Decompression of the high pressure groups lasted 15 min. After decapitation, samples of the frontal cortex and the striatum were taken, weighed, washed, and then incubated in Krebs-Ringer bicarbonate for 1 h. The release of eicosanoids in the medium was determined by enzyme immunoassay. Mild hyperoxia only significantly reduced in the striatum the release of 6-keto-PGF1 alpha (1.3 +/- 2.4 vs 10.9 +/- 6.6 pg/mg wet tissue, p < 0.001; mean +/- SD) and PGE2 (3.2 +/- 2.7 vs 7.8 +/- 6.5 pg/mg wet tissue, p < 0.05), whereas TXB2 did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Chem Neuropathol 1993 Oct
PMID:Effect of hyperbaric oxygen on prostaglandin and thromboxane synthesis in the cortex and the striatum of rat brain. 829 21

The proliferative action of prostaglandin E2 in a rat osteoblastic cell line was studied. Prostaglandin E2 has a crucial effect on bone remodeling process and is shown to stimulate protein and DNA synthesis in serum depleted condition. This reaction is completely inhibited by protein kinase C inhibitors, suggesting that protein kinase C activation induced by prostaglandin E2 is involved in the proliferative response of osteoblast cells.
Biochem Mol Biol Int 1993 Apr
PMID:Involvement of protein kinase C in proliferative response of osteoblastic cell lines stimulated with prostaglandin E2. 833 10

To examine the possible role of basic fibroblast growth factor (FGF) in regulating the effects of TNF alpha, we tested the effect of FGF on TNF alpha-mediated PGE2 production and TNF alpha receptor expression in human fibroblasts. We found that, while FGF alone had no effect on PGE2 production, it enhanced the amount of PGE2 produced in response to TNF alpha between 3 and 11-fold. FGF stimulated TNF alpha-induced PGE2 production independent of potential TNF alpha-mediated IL-1 production, as neither anti-IL-1 mAbs nor IL-1 receptor antagonist protein (IRAP) inhibited TNF alpha induced-PGE2 production or the stimulatory effect of FGF. A one minute exposure of cells to FGF prior to removal was sufficient to significantly enhance TNF alpha-induced PGE2 production; the maximal FGF effect was reached after a 6 h preincubation. We also found that FGF significantly enhanced TNF alpha receptor expression. Untreated fibroblasts expressed approximately 3,900 receptors/cell, while cells treated with FGF for 6 h expressed approximately 9,500 receptors/cell, a 2.4-fold increase in receptor number; there was no apparent change in affinity for TNF alpha (Kd 3.8 x 10(-11) M). The FGF-mediated increase in TNF alpha receptor expression and TNF alpha-mediated PGE2 production could be abolished by FGF mAbs, indicating a specific FGF effect. These results show that FGF increases TNF alpha receptor expression and suggest that this may account, at least in part, for the ability of FGF to enhance TNF alpha-mediated PGE2 production in human fibroblasts.
Mol Cell Biochem 1993 Mar 10
PMID:Fibroblast growth factor increases TNF alpha-mediated prostaglandin E2 production and TNF alpha receptor expression in human fibroblasts. 838 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>