ArticleProceedings. Biological sciences2013
Functional evidence for physiological mechanisms to circumvent neurotoxicity of cardenolides in an adapted and a non-adapted hawk-moth species.
Article in Proceedings. Biological sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 72 citations in OpenAlex.
- Integrated Toxicokinetics Underlie Selective Sequestration of Cardiotonic Steroids in an Asian Snake Rhabdophis tigrinus.Journal of chemical ecology · 2026Article
- Tetraopes Milkweed Beetle Genomes Elucidate the Adaptive Basis of a Temperate Coevolutionary Radiation.Molecular ecology resources · 2026Article
- Genomic basis of adaptation to cardiac glycosides in three insect orders.Frontiers in genetics · 2026Article
- Evolutionary insights into NaBMC ecology and evolution · 2025Article
- Regionality and Temporal Dynamics of Sequestration and Relocation of Cardenolides in the Monarch Butterfly, Danaus plexippus.Journal of chemical ecology · 2025Article
- Plant chemical diversity enhances defense against herbivory.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Substrate Specificity of ABCB Transporters Predicted by Docking Simulations Can Be Confirmed by Experimental Tests.Molecules (Basel, Switzerland) · 2024Article
- Article
- Fecal Deployment: An Alternative Way of Defensive Host Plant Cardenolide Use by Lilioceris merdigera Larvae.Journal of chemical ecology · 2024Article
- Predatory fireflies and their toxic firefly prey have evolved distinct toxin resistance strategies.Current biology : CB · 2023Article
- Predatory fireflies and their toxic firefly prey have evolved distinct toxin resistance strategies.bioRxiv : the preprint server for biology · 2023Article
- Polyphagous insectHeliyon · 2022Article
- Metabolization and sequestration of plant specialized metabolites in insect herbivores: Current and emerging approaches.Frontiers in physiology · 2022Review
- Less Is More: a Mutation in the Chemical Defense Pathway of Erysimum cheiranthoides (Brassicaceae) Reduces Total Cardenolide Abundance but Increases Resistance to Insect Herbivores.Journal of chemical ecology · 2020Article
- ABCB transporters in a leaf beetle respond to sequestered plant toxins.Proceedings. Biological sciences · 2020Article
- Article
- Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo.eLife · 2019Article
- Predictability in the evolution of Orthopteran cardenolide insensitivity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Insect ATP-Binding Cassette (ABC) Transporters: Roles in Xenobiotic Detoxification and Bt Insecticidal Activity.International journal of molecular sciences · 2019Review
- Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.