Selective inhibition of group II phospholipase A2 by quercetin.
The influence of quercetin, chlorpromazine, aristolochic acid, and indomethacin on group I phospholipase A2 (PLA2) from porcine pancreas and on group II PLA2 from Vipera russelli was compared. Quercetin and chlorpromazine were found to inhibit PLA2 activity in lower concentrations (< 100 microM), while aristolochic acid and indomethacin were inhibitory only in higher concentrations (> 100 microM). The order of potency against Vipera PLA2 was: quercetin > chlorpromazine > aristolochic acid > indomethacin, while the order of potency against pancreatic PLA2 was: chlorpromazine > aristolochic acid > indomethacin >> quercetin. Thus, quercetin was a potent inhibitor towards group II PLA2 (IC50 = 2 microM), but a very weak inhibitor against group I PLA2, with maximum 30% inhibition. Aristolochic acid and indomethacin were three to four times more potent towards group II PLA2 than towards group I PLA2, while chlorpromazine was equally potent towards the two PLA2 types. Quercetin and chlorpromazine were also tested against two PLA2 fractions purified from the plasma of septic shock patients; chlorpromazine was then equally potent towards the two PLA2 fractions, whereas quercetin was a potent inhibitor of only one of the two PLA2 fractions (IC50 = 4 microM). Together, these results indicate that (1) different PLA2 inhibitors have different potency depending on which type of PLA2 they are used against, (2) quercetin selectively inhibits group II PLA2 and may therefore be used to discriminate between different PLA2 forms in biological materials, and (3) both PLA2 of group I and group II are present in septic shock plasma.
Lindahl
M
M
Department of Clinical Chemistry, University of Linköping, Sweden.
Tagesson
C
C
D000818:Animals; D034341:Aristolochic Acids; D002746:Chlorpromazine / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000097:blood; D054467:Phospholipases A2; D011794:Quercetin / Q000494:pharmacology*; D012772:Shock, Septic / Q000201:enzymology; D013379:Substrate Specificity; D013552:Swine; D014757:Viper Venoms / Q000201:enzymology
D034341:Aristolochic Acids; D010616:Phenanthrenes; D014757:Viper Venoms; C000228:aristolochic acid I; D011794:Quercetin; D010741:Phospholipases A; D054467:Phospholipases A2; D002746:Chlorpromazine; D007213:Indomethacin