Verbrauchskoagulopathie

Ludwig, Hans

doi:10.1007/bf02429762

Cited by 4 publications

(2 citation statements)

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“…An increase in intracellular calcium results in activation of phospholipase A2 which catalyzes the hydrolysis of the fatty acid ester linkage at position 2 of the phospholipid molecule, generating arachidonic acid and lysoPAF (4). Eicosanoids can be synthesized from arachidonic acid and, furthermore, through action of another calcium dependent enzyme, acetyltransferase, lysoPAF can be converted to PAF (9), with resultant inflammatory and hemodynamic effects that may be important in disease processes (5). By preventing calcium influx in response to biologically relevant mediators, the calcium channel blockers may prevent generation of these inflammatory mediators and thus provide protection from tissue injury in various pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…It is synthesized by various activated cell types, including vascular endothelial cells {7), and has a broad spectrum of inflammatory and hemodynamic actions that may be important in disease states (6,8}. Based on in vitro studies, it is clear that the synthesis of PAF is dependent on the presence of extracellular calcium (9), and that transmembrane calcium flux is the signal that initiates PAF synthesis (10). This most likely reflects the calcium-dependence of two key enzymes in the PAF synthetic pathway, phospholipase A2 and acetyltransferase (9,11 ).…”

Section: Lipids 26 1218-1222 (1991)mentioning

confidence: 99%

See 1 more Smart Citation

Calcium Channel Blockade Inhibits Platelet Activating Factor Production by Human Umbilical Vein Endothelial Cells

Tolins¹,

Melemed²,

Sulciner³

et al. 1992

Platelet-Activating Factor and Structurally Related Alkyl Ehter Lipids

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An increase in intracellular calcium level is an important signal in the regulation of cellular responses under normal and pathological conditions. Because two key enzymes in the synthetic pathway of platelet activating factor (PAF), phosphollpase A 2 and acetyltransferase, are calcium dependent, we hypothesized that calcium channel blockade may inhibit agonist-induced PAF synthesis. Primary cultures of human umbilical vein endothelial cells (EC), pre-incubated with [3H]acetate, were exposed to thrombin (5 U/mL) and PAF production was quantitated by incorporation of radiolabel into the EC lipid fraction co-migrating with exogenous PAF in thin-layer chromatography. The effect of pre-incubation with calcium channel blockers (verapamil, diltiazem, 10-4 M) or buffer was determined. Results (triplicate experiments, * P<0.05 vs buffer, t P<0.05 vs thrombin) demonstate that pre-incubation with calcium channel blocker markedly inhibits thrombin-induced PAF production (verapamil:buffer 273 +_ 122, thrombin 10,735 ___ 1524", thrombin + verap-mll 178 +_ 91 t cpm/plate; diltiazem:buffer 1097 +__ 581, thrombin 15,283 +__ 2661", thrombin + dlltiazem 280 ___ 56 ~ cpm/plate). The effect of diltiazem was dosedependent (% inhibition: 10 -7 M, 46%; 10-5 M, 60%; 10 -4 M, 98%). Diltiazem also inhibited bradykinin (10-s M) induced PAF synthesis. In calcium-free medium or in the presence of LaCI 3 (10 -3 M}, the PAF response of EC to thrombin was blunted (buffer 582 ___ 360, thrombin 5394 + 1069, thrombin Jr calcium free medium 1055 ___ 571, thrombin -b LaC13 1271 ----. 58 cpm/plate). We conclude that calcium channel blockers prevent agonistinduced PAF synthesis, possibly by preventing cellulax calcium influx and activation of PAF synthetic enzymes. We speculate that this mechanism may underlie, at least in part, the beneficial effect of calcium channel blockade under various pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Lipids 26 1218-1222 (1991)mentioning

confidence: 99%