Oral toxicity to flesh flies of a neurotoxic polypeptide

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Abstract
An insect selective neurotoxic polypeptide from venom of the scorpion Androctonus australis (AalT, Mr 8,000) was shown to cross the midgut of the flesh fly Sarcophaga falculata, using assays of oral toxicity, column chromatography, and microscopic autoradiography of the native and radioiodinated toxin. AalT induced paralysis of flies within 1–2 h after oral administration, with a lethal dose (LD50) of 10 μg/100 mg of body weight. Oral toxicity was about 0.14% of toxicity by injection. Hemolymph collection 70–85 min after feeding flies with [125l]AalT showed that 5% of ingested radioactivity appeared in hemolymph. Most of this represented degradation products, but included about 0.3% of the chromatographically intact toxin. In contrast, hemolymph of identically treated lepidopterous larvae (Manduca, Helioverpa [=Heliothis]) contained degradation products but no intact toxin. [125l]AalT was shown to cross the midgut of Sarcophaga through a morphologically distinct segment of the midgut previously shown to be permeable to a cytotoxic, positively charged polypeptide of similar molecular weight. These results suggest that Sarcophaga midgut contains a morphologically and functionally distinct segment that transports small peptides, and that employment of neurotoxic polypeptides for insect control may be feasible. Activity might be greatly improved through modification and metabolic stabilization of active peptides.