Affiliation:
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
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.
Subject
General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
50 articles.
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