STRUCTURE-ACTIVITY OF THREE PHOSPHOLIPID ANALOGUES TOWARDS INHIBITION OF PHOSPHOLIPASE A2 IN MACROPHAGES

• Published in: Pharmacological research Vol. 35; no. 1; pp. 73 - 78
• Main Authors: LETOURNEUX, Y., BOURASS, J., BOUCROT, P., ELKIHEL, L., PETIT, J.Y.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-01-1997
• Subjects: Acetophenones - pharmacology; Animals; Anti-Inflammatory Agents - pharmacology; arachidonic acid; Cells, Cultured; Culture Media; Dexamethasone - pharmacology; eicosanoid; Eicosanoids - pharmacology; Enzyme Inhibitors - pharmacology; macrophage; Macrophages, Peritoneal - enzymology; Male; phospholipase A2; Phospholipases A - antagonists & inhibitors; Phospholipases A2; phospholipid analogue; Phospholipids - chemical synthesis; Phospholipids - metabolism; Phospholipids - pharmacology; Quinacrine - pharmacology; Rats; Structure-Activity Relationship; Tritium; arachidonic acid; eicosanoid; macrophage; phospholipid analogue; phospholipase A2
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1996.0107

At concentrations 1–20gmMin culture medium of rat peritoneal macrophages which were stimulated with ionophore A23187, the phospholipid analogues 1-decyl-2-octyl-glycero- phosphocholine and 1-dodecyl-2-octanamido-2-deoxy glycerophosphocholine were found more potent inhibitors than 1-octyl-2-octylthio-2-deoxy glycerophosphocholine to lower the phospholipase A2activities. The inhibitory effect was measured by [3H] eicosatetraenoic acid ([3H]20:4) release in macrophages and extracellular fluids and synthesis of [3H] eicosanoids after incubation of macrophages with traces of the molecular species of lecithin 1-octadecanoyl-2-[3H] eicosatetraenoyl glycerophosphocholine. The three phospholipid analogues developed higher inhibitory effects than mepacrine, dexamethasone or bromophenacyl bromide, at corresponding concentrations in medium.