THE MECHANISM OF ACTION OF AVERMECTINS IN CAENORHABDITIS-ELEGANS - CORRELATION BETWEEN ACTIVATION OF GLUTAMATE-SENSITIVE CHLORIDE CURRENT, MEMBRANE-BINDING, AND BIOLOGICAL-ACTIVITY

Xenopus laevis oocytes were injected with mRNA isolated from the free-living nematode Caenorhabditis elegans and the activation and potentiation of a glutamate-sensitive chloride current by a series of avermectin analogs and milbemycin D were determined. There was a strong correlation between the EC(50) value determined for current activation in oocytes, the LD(95) value for nematocidal activity, and also for the K-i value determined in a [H-3]ivermectin competition binding assay. Four of the analogs were tested for potentiation of glutamate-sensitive current and the rank order for potentiation correlated with the EC(50) for direct activation of current. We conclude that avermectins and milbemycins mediate their nematocidal effects on C. elegans via an interaction with a common receptor molecule, glutamate-gated chloride channels.