期刊
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 280, 期 1759, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rspb.2012.3089
关键词
cardenolides; Daphnis nerii; Manduca sexta; P-glycoprotein; Na+K+-ATPase; resistance
资金
- Studienstiftung des deutschen Volkes
- Deutsche Forschungsgemeinschaft [Do527/5-1]
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 radio-active-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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