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 potentia tion of a glutamate-sensitive chloride current by a series of avermect in analogs and milbemycin D were determined. There was a strong correl ation between the EC(50) value determined for current activation in oo cytes, 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 cu rrent and the rank order for potentiation correlated with the EC(50) f or direct activation of current. We conclude that avermectins and milb emycins mediate their nematocidal effects on C. elegans via an interac tion with a common receptor molecule, glutamate-gated chloride channel s.