BASIS FOR SELECTIVE ACTION OF A SYNTHETIC MOLTING HORMONE AGONIST, RH-5992 ON LEPIDOPTERAN INSECTS

The non-steroidal ecdysone agonist, RH-5992, induces a precocious inco mplete molt in lepidopteran insects but is refractory to insects of ot her orders. We used two lepidopteran cell lines, FPMI-CF-203 (CF-203) and IPRI-MD-66 (MD-66) and two dipteran cell lines, DM-2 and K-c, to i nvestigate the lepidopteran specificity of RH-5992. The mRNAs for horm one receptor 3 homologues cloned from Drosophila (DHR3) and Choristone ura (CHR3) are directly induced by 20-hydroxydecdysone (20E) and serve as suitable markers for studying ecdysone action. Dose response exper iments showed that 10(-7) M 20E induced CHR3 mRNA in CF-203 cells and DHR3 mRNA in DM-2 cells. Concentrations of RH-5992 as low as 10(-10) M induced CHR3 mRNA in CF-203 cells, whereas concentrations as high as 10(-6) M induced only very low levels of DHR3 mRNA in DM-2 cells. Stud ies using C-14- RH-5992 revealed that lepidopteran cell lines (CF-203 and MD-66) retained more of this compound within the cells than the di pteran cell lines (DM-2 and K-c). The clearance of RH-5992 from DM-2 c ells was temperature dependent and was blocked by 10(-5) M ouabain, an inhibitor of Na+, K+-ATPase suggesting that the efflux was due to act ive transport. (C) 1998 Elsevier Science Ltd. All rights reserved.