Functional evidence for physiological mechanisms to circumvent neurotoxicity of cardenolides in an adapted and a non-adapted hawk-moth species |
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Authors: | Georg Petschenka Christian Pick Vera Wagschal Susanne Dobler |
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Institution: | 1.Molekulare Evolutionsbiologie, Biozentrum Grindel, Martin-Luther-King-Platz 3, 20146 Hamburg, Germany;2.Tierphysiologie, Biozentrum Grindel, Martin-Luther-King-Platz 3, 20146 Hamburg, Germany |
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Abstract: | Because cardenolides specifically inhibit the Na+K+-ATPase, insects feeding on cardenolide-containing plants need to circumvent this toxic effect. Some insects such as the monarch butterfly rely on target site insensitivity, yet other cardenolide-adapted lepidopterans such as the oleander hawk-moth, Daphnis nerii, possess highly sensitive Na+K+-ATPases. Nevertheless, larvae of this species and the related Manduca sexta are insensitive to injected cardenolides. By radioactive-binding assays with nerve cords of both species, we demonstrate that the perineurium surrounding the nervous tissue functions as a diffusion barrier for a polar cardenolide (ouabain). By contrast, for non-polar cardenolides such as digoxin an active efflux carrier limits the access to the nerve cord. This barrier can be abolished by metabolic inhibitors and by verapamil, a specific inhibitor of P-glycoproteins (PGPs). This supports that a PGP-like transporter is involved in the active cardenolide-barrier of the perineurium. Tissue specific RT-PCR demonstrated expression of three PGP-like genes in hornworm nerve cords, and immunohistochemistry further corroborated PGP expression in the perineurium. Our results thus suggest that the lepidopteran perineurium serves as a diffusion barrier for polar cardenolides and provides an active barrier for non-polar cardenolides. This may explain the high in vivo resistance to cardenolides observed in some lepidopteran larvae, despite their highly sensitive Na+K+-ATPases. |
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Keywords: | cardenolides Daphnis nerii Manduca sexta P-glycoprotein Na+K+-ATPase resistance |
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