Thrombin and tryptase stimulation of human bladder microvascular endothelial cells (Cambrex Bioscience, Walkersville, Maryland) results in the production of multiple membrane phospholipid derived ...inflammatory mediators via the activation of a calcium independent phospholipase A2 that may have important implications in bladder inflammatory conditions, such as interstitial cystitis. We examined the effect of multiple phospholipase A2 and cyclooxygenase inhibitors on the immediate release of prostacyclin from human bladder microvascular endothelial cells.
We stimulated confluent human bladder microvascular endothelial cell monolayers with thrombin or tryptase and measured the immediate release of prostacyclin. Human bladder microvascular endothelial cells were pretreated with several selective phospholipase A2 and cyclooxygenase inhibitors before thrombin or tryptase stimulation to determine which combination of phospholipase A2/cyclooxygenase isoforms was involved in this process. Phospholipase A2 activity was measured using (16:0, 3H18:1) plasmenylcholine substrate in the absence of calcium. 3H arachidonic acid release was measured in the surrounding medium from prelabeled human bladder microvascular endothelial cell monolayers. Prostacyclin release into the surrounding medium was measured using a commercially available immunoassay kit.
The immediate increase in prostacyclin release from thrombin or tryptase stimulated human bladder microvascular endothelial cells depended on the activation of membrane associated calcium independent phospholipase A2, resulting in an increase in arachidonic acid production. Constitutively active cyclooxygenase-1 was then responsible for further metabolism of free arachidonic acid to prostacyclin.
These results show that the search for a suitable anti-inflammatory agent that selectively target specific phospholipase A2 isoforms requires rigorous testing in several cell types in response to various stimuli.
A new synthesis of 2-pyridineacetamides was developed starting from pyran-2-one
N-functionalized amidines
4
. Secondary amines reacted in a sealed tube with amidines
4
and, by nucleophilic attack on ...pyran-2-one nucleus and thermal rearrangement, afforded exclusively the 2-pyridineacetamide derivatives
6
or a mixture of amide compounds
6
and
7
depending on the substituents linked to C-α of the starting amidine
4
.
Graphic
Several new thiophene, thiazole, 2H-pyran-2-one, benzimidazo1,2-apyridine and pyridine derivatives were synthesised from active methylene reagents, 4-chloroacetylantipyrine and enaminones as starting ...materials.
The reaction of 8-hydroxy-1,3-dimethyl-4H-cycloheptacfuran-4-one with the ethoxymethylene derivatives of malononitrile or ethyl cyanoacetate in the presence of KOH gave noncyclic cyanovinyl ...derivatives as their potassium salts rather than the expected α-pyrone derivatives. They are smoothly cyclized to the target α-pyrones by refluxing with acid. The corresponding 3-benzamido-2H-pyran-2-ones can be obtained in a single vessel from the 2-aryl-4-ethoxymethylene-4H-1,3-oxazol-5-ones using the same scheme.
Synthesis and physico-chemical properties of 4-alkoxyphenyl and 4-alkoxybiphenyl-4′-yl 2H-pyran-2-one-5-carboxylates, 2H-chromen-2-one-6-yl 4-alkoxybenzoates and 4-alkoxybiphenyl-4′-carboxylates, and ...2H-chromen-2-one-7-yl 4-alkoxybenzoates and 4-alkoxybiphenyl-4′-carboxylates are described. Terminal 2H-pyran-2-one and chromen-2-one cores are effective in enhancing liquid crystalline properties. The layer structure was examined by a small angle X-ray measurement, and the results are discussed in terms of the molecular structure. The polar effect of the terminal lactone group is recognized in the thermal properties and the layer structure of smectic A (SmA) phase.
Five new components, named multiforisins A, B, C, D, and E, with immunosuppressive activity were isolated from an Ascomycete, Gelasinospora multiforis. Multiforisin A, the main immunosuppressive ...principle of this fungus, was deduced to be 5-formyl-3-(hydroxymethyl)-4-methoxy-6-(1E-propenyl)-α-pyrone. Multiforisins B, C, D, and E were also deduced to be α-pyrone derivatives related to multiforisin A. The IC50 values of multiforisins A, B, C, D, E, and dihydro multiforisin A were evaluated against proliferation of mouse spleen lymphocytes stimulated with concanavalin A and lipopolysaccharide.
The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dihydro-5,6-dehydrokawain was isolated by a simple ...method without chromatography from the leaves of Alpinia speciosa K. Schum. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents.
Among the synthesized compounds, dimethyl 6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl phosphorothionate (4) had the strongest antifungal activity of 91% at 100 ppm against Corticium rolfsii.
The mechanisms underlying arachidonic acid (AA) release by uterine stromal (UIII) cells were studied. Stimulation of AA release by calcium ionophore and PMA are inhibited by various PKC inhibitors ...and by calcium deprivation. These results suggest the involvement of an AA‐specific cPLA2 as the release of docosahexaenoic acid (DHA) from prelabelled cells is much lower than the release of AA. The results also show a more original stimulation of AA and DHA release induced by PKC inhibitors, which is insensitive to calcium deprivation. This stimulation is not due to acyltransferase inhibition, suggesting the participation of a Ca2+‐independent PLA2 (iPLA2). However, iPLA2 activity measured in UIII cells is inhibited by the specific iPLA2 inhibitor, BEL, and is not stimulated by PKC inhibitors, in contrast with the AA and DHA release. It seems therefore that this iPLA2 cannot be involved in this mechanism. The participation of another iPLA2, BEL‐insensitive, is discussed.
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