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Selective mechanism of action of tebufenozide on lepidopteran cell lines

The non-steroidal ecdysone agonist, tebufenozide (RH-5992), induces a precocious incomplete molt primarily on lepidopteran insects, but has little or no effect on insects of other orders. 20 Hydroxyecdysone at 10 -7 M induced the transcription factor CHR3 mRNA in CF-203 cells and DHR3 mRNA in DM-2 cells. Tebufenozide even at 10 -10 M induced CHR3 mRNA in lepidopteran CF-203 cells, but even at 10 -5 M it induced only trace levels of DHR3 mRNA in dipteran DM-2 cells. Studies using radiolabelled RH-5992 revealed that lepidopteran cell lines (CF-203 and MD-66) retained more of this compound within the cells than dipteran cell lines (DM-2 and K c ). The efflux of radiolabelled RH-5992 from DM-2 cells was temperature-dependent and was blocked by 10 -5 M ouabain, an inhibitor of Na + , K + -ATPase, suggesting that the efflux was due to active transport.