ArticleInsect biochemistry and molecular biology2017
Multidrug transporters and organic anion transporting polypeptides protect insects against the toxic effects of cardenolides.
Article in Insect biochemistry and molecular biology, 2017. 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, 54 citations in OpenAlex.
- Integrated Toxicokinetics Underlie Selective Sequestration of Cardiotonic Steroids in an Asian Snake Rhabdophis tigrinus.Journal of chemical ecology · 2026Article
- Toxin resistance in the monarch butterfly expanded its milkweed host range.bioRxiv : the preprint server for biology · 2026Article
- Tetraopes Milkweed Beetle Genomes Elucidate the Adaptive Basis of a Temperate Coevolutionary Radiation.Molecular ecology resources · 2026Article
- Dietary Fructose and Palmitic Acid Induce Shared and Divergent Transcriptional Responses in the Larval Midgut ofCurrent issues in molecular biology · 2026Article
- Selective Sequestration of Cardenolides Shapes Chemical Defense in an Aposematic Butterfly.Journal of chemical ecology · 2026Review
- Genomic basis of adaptation to cardiac glycosides in three insect orders.Frontiers in genetics · 2026Article
- Genetic architecture of resistance to plant secondary metabolites in Photorhabdus entomopathogenic bacteria.BMC genomics · 2025Article
- Regionality and Temporal Dynamics of Sequestration and Relocation of Cardenolides in the Monarch Butterfly, Danaus plexippus.Journal of chemical ecology · 2025Article
- Entomopathogenic Nematode Species Vary in Their Behavior and Virulence in Response to Cardiac Glycosides Within and Around Insect Hosts.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
- 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
- Tissue-specific plant toxins and adaptation in a specialist root herbivore.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Defence mitigation by predators of chemically defended prey integrated over the predation sequence and across biological levels with a focus on cardiotonic steroids.Royal Society open science · 2022Review
- Trade-offs between cost of ingestion and rate of intake drive defensive toxin use.Biology letters · 2022Article
- Evolution in small steps and giant leaps.Evolution; international journal of organic evolution · 2022Review
- Tick Saliva and Salivary Glands: What Do We Know So Far on Their Role in Arthropod Blood Feeding and Pathogen Transmission.Frontiers in cellular and infection microbiology · 2021Review
- The Nuclear Receptor Seven Up Regulates Genes Involved in Immunity and Xenobiotic Response in the AdultG3 (Bethesda, Md.) · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
In the struggle against dietary toxins, insects are known to employ target site insensitivity, metabolic detoxification, and transporters that shunt away toxins. Specialized insects across six taxonomic orders feeding on cardenolide-containing plants have convergently evolved target site insensitivity via specific amino acid substitutions in the Na/K-ATPase. Nonetheless, in vitro pharmacological experiments have suggested a role for multidrug transporters (Mdrs) and organic anion transporting polypeptides (Oatps), which may provide a basal level of protection in both specialized and non-adapted insects. Because the genes coding for these proteins are evolutionarily conserved and in vivo genetic evidence in support of this hypothesis is lacking, here we used wildtype and mutant Drosophila melanogaster (Drosophila) in capillary feeder (CAFE) assays to quantify toxicity of three chemically diverse, medically relevant cardenolides. We examined multiple components of fitness, including mortality, longevity, and LD50, and found that, while the three cardenolides each stimulated feeding (i.e., no deterrence to the toxin), all decreased lifespan, with the most apolar cardenolide having the lowest LD50 value. Flies showed a clear non-monotonic dose response and experienced high levels of toxicity at the cardenolide concentration found in plants. At this concentration, both Mdr and Oatp knockout mutant flies died more rapidly than wildtype flies, and the mutants also experienced more adverse neurological effects on high-cardenolide-level diets. Our study further establishes Drosophila as a model for the study of cardenolide pharmacology and solidifies support for the hypothesis that multidrug and organic anion transporters are key players in insect protection against dietary cardenolides.
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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.