Cytochrome P‐450 Inducers and Inhibitors Interfering with Ecdysone 20‐Monooxygenases and Their Activities during Postembryonic Development of Neobellieria bullata Parker

Abstract

AbstractThe cytochrome P‐450‐dependent microsomal and mitochondrial ecdysone 20‐monooxygenase systems convert ecdysone into 20‐hydroxyecdysone. The microsomal fraction of fat bodies of zero h wandering stage fleshfly larvae (Neobellieria bullata; Diptera: Sarcophagidae) has a high ecdysone 20‐ monooxygenase activity. The effects of cytochrome P‐450 inhibitors were investigated in vitro on microsomal ecdysone 20‐monooxygenase. Metyrapone, fenarimol and certain imidazole derivatives (KK‐42, KK‐110, KK‐135 and PIM) are strong inhibitors. The IC50 value of KK‐110, which is the strongest inhibitor, is 2 × 10−7 M. A triazolyl and two cyclopropylamine derivatives have low activity. The activities of different NADPH‐cytochrome c (P‐450) reductase inhibitors were also assessed; diquat dibromide is a moderate inhibitor of microsomal ecdysone 20‐monooxygenase, while paraquat dichloride has no activity.In‐vivo experiments with cytochrome P‐450 inducers and inhibitors gave the following results: (a) fenarimol, FI‐121, precocene‐2 caused “permanent” first‐instar larvae; (b) barbital, phenobarbital and their sodium salts caused significant delay in larval development; (c) PIM, PTM, metyrapone, KK‐42, KK‐135, J‐2710, RH 5849 and colchicine caused moulting disturbances; (d) J‐2710, PIM, PTM, KK‐42, KK‐135, RH 5849 and colchicine caused lethal spiracle and mandible malformation; (e) KK‐110, fenarimol, barbital and phenobarbital caused precocious pupariation.