| pubmed-article:8185681 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0027950 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0031667 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C1999216 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:8185681 | lifeskim:mentions | umls-concept:C0141678 | lld:lifeskim |
| pubmed-article:8185681 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:8185681 | pubmed:dateCreated | 1994-6-15 | lld:pubmed |
| pubmed-article:8185681 | pubmed:abstractText | Scalaradial, a marine natural product with anti-inflammatory activity, has been shown to be a selective inhibitor of 14 kDa type II phospholipase A2(PLA2). We have examined the inhibition by scalaradial (0.1 nM to 10 microM) of neutrophil function (degranulation) in response to receptor-mediated activation [N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), 30 nM; leuokotriene B4 (LTB4), 100 nM; platelet-activating factor (PAF), 100 nM] and non-receptor-mediated stimuli [A23187 (1 microM) and thapsigargin (100 nM)]. Furthermore, we evaluated the ability of scalaradial to inhibit the increase in intracellular Ca2+ in response to fMLP, LTB4, A23187, and thapsigargin as well as its ability to prevent either fMLP- or LTB4-mediated elevation in inositol phosphate production (InsP). Scalaradial was a potent inhibitor of both receptor- (IC50 = 50-200 nM) and non-receptor- (IC50 = 40-900 nM) mediated degranulation. Although scalaradial inhibited the mobilization of Ca2+ induced by fMLP, LTB4, and PAF, it did not affect the maximal Ca2+ levels attained with A23187 or thapsigargin. Neutrophil-binding studies with [3H]fMLP and [3H]LTB4 would suggest that the effect of scalaradial on agonist-induced degranulation and increase in intracellular Ca2+ was not at the receptor level because 50-fold higher concentrations were required to have a significant effect on the binding of these agonists. To determine if scalaradial affected phosphatidylinositol selective phospholipase C (PI-PLC) activity, assays were conducted to monitor fMLP- and LTB4-induced formation of InsPs using myo-[3H]inositol-labeled U-937 cells. In these cells, 2.5 to 9-fold higher concentrations of scalaradial were required to inhibit PI-PLC activity than to inhibit agonist-induced degranulation of neutrophils, suggesting that the effects of scalaradial on Ca2+ and degranulation are not the sole result of blocking receptor activation of PI-PLC. Results obtained with receptor-mediated stimuli suggest that scalaradial may have direct effects on Ca2+ channels and InsP turnover, but inhibition of intracellular Ca2+ levels was not required for scalaradial to block degranulation since scalaradial was capable of inhibiting degranulation produced by either A23187 or thapsigargin, without changing the maximal Ca2+ levels obtained with these two stimuli. These results demonstrate that scalaradial can inhibit degranulation in the presence of micromolar intracellular Ca2+ concentration, thus supporting the hypothesis that a 14 kDa PLA2 may be important in the regulation of neutrophil degranulation. | lld:pubmed |
| pubmed-article:8185681 | pubmed:language | eng | lld:pubmed |
| pubmed-article:8185681 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8185681 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:8185681 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:8185681 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:8185681 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:8185681 | pubmed:issn | 0006-2952 | lld:pubmed |
| pubmed-article:8185681 | pubmed:author | pubmed-author:SarauH MHM | lld:pubmed |
| pubmed-article:8185681 | pubmed:author | pubmed-author:FoleyJ JJJ | lld:pubmed |
| pubmed-article:8185681 | pubmed:author | pubmed-author:RuseGG | lld:pubmed |
| pubmed-article:8185681 | pubmed:author | pubmed-author:MarshallL ALA | lld:pubmed |
| pubmed-article:8185681 | pubmed:author | pubmed-author:SchmidtD BDB | lld:pubmed |
| pubmed-article:8185681 | pubmed:author | pubmed-author:BarnetteM SMS | lld:pubmed |
| pubmed-article:8185681 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:8185681 | pubmed:day | 29 | lld:pubmed |
| pubmed-article:8185681 | pubmed:volume | 47 | lld:pubmed |
| pubmed-article:8185681 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:8185681 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:8185681 | pubmed:pagination | 1661-7 | lld:pubmed |
| pubmed-article:8185681 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:8185681 | pubmed:year | 1994 | lld:pubmed |
| pubmed-article:8185681 | pubmed:articleTitle | Effects of scalaradial, a novel inhibitor of 14 kDa phospholipase A2, on human neutrophil function. | lld:pubmed |
| pubmed-article:8185681 | pubmed:affiliation | Department of Inflammation and Respiratory Pharmacology, SmithKline Beecham Laboratories, King of Prussia, PA 19406. | lld:pubmed |
| pubmed-article:8185681 | pubmed:publicationType | Journal Article | lld:pubmed |
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