Phospholipase A2--regulation and inhibition.
Phospholipase A2 (PLA2) has been implicated in the pathogenesis of different diseases. Thus, the pharmacological intervention of PLA2 activity by specific inhibitors is of great therapeutical value in ameliorating pathological conditions. Despite a great number of published data regarding PLA2 inhibitors none has reached clinical application. Since enzyme activity can be greatly influenced by the experimental conditions of the test system used, a potent in vitro enzyme inhibitor does not indicate therapeutic effectiveness per se. In order to enhance the predictable value of an in vitro screening system for PLA2 inhibitors, a battery of test systems each measuring certain parameters should be applied. Considering the complex mechanism(s) of PLA2 it is extremely important to elucidate the exact inhibition mechanism of those compounds, which have passed these first filters. True inhibitors of PLA2 should then be evaluated in suitable ex vivo, in vivo models.
Scheuer
W
W
Boehringer Mannheim GmbH, Forschung Biochemie, Penzberg.
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010179:Pancreas / Q000201:enzymology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000502:physiology; D054467:Phospholipases A2; D013552:Swine
D002738:Chloroquine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002746:Chlorpromazine