PloS one, 2013-05, Vol.8 (5), p.e64905
2013
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- Autor(en) / Beteiligte
- Titel
- Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels
- Ist Teil von
- PloS one, 2013-05, Vol.8 (5), p.e64905
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Mosquito-borne diseases such as malaria and dengue fever take a large toll on global health. The primary chemical agents used for controlling mosquitoes are insecticides that target the nervous system. However, the emergence of resistance in mosquito populations is reducing the efficacy of available insecticides. The development of new insecticides is therefore urgent. Here we show that VU573, a small-molecule inhibitor of mammalian inward-rectifying potassium (Kir) channels, inhibits a Kir channel cloned from the renal (Malpighian) tubules of Aedes aegypti (AeKir1). Injection of VU573 into the hemolymph of adult female mosquitoes (Ae. aegypti) disrupts the production and excretion of urine in a manner consistent with channel block of AeKir1 and renders the mosquitoes incapacitated (flightless or dead) within 24 hours. Moreover, the toxicity of VU573 in mosquitoes (Ae. aegypti) is exacerbated when hemolymph potassium levels are elevated, suggesting that Kir channels are essential for maintenance of whole-animal potassium homeostasis. Our study demonstrates that renal failure is a promising mechanism of action for killing mosquitoes, and motivates the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0064905Titel-ID: cdi_plos_journals_1357024119
- Format
- –
- Schlagworte
- Aedes - genetics, Aedes - growth & development, Aedes - metabolism, Aedes aegypti, Agrochemicals, Anesthesiology, Animals, Anopheles - growth & development, Anopheles - metabolism, Aquatic insects, Benzimidazoles - chemistry, Benzimidazoles - metabolism, Benzimidazoles - pharmacology, Biology, Channels, Chemical agents, Chemistry, Culex - growth & development, Culex - metabolism, Culicidae, Dengue, Dengue fever, Dose-Response Relationship, Drug, Excretion, Female, Fever, Global health, HEK293 Cells, Hemolymph, Hemolymph - drug effects, Hemolymph - metabolism, Homeostasis, Humans, Imines - chemistry, Imines - metabolism, Imines - pharmacology, Inhibitors, Insect Proteins - antagonists & inhibitors, Insect Proteins - genetics, Insect Proteins - physiology, Insecticide resistance, Insecticides, Insecticides - chemistry, Insecticides - pharmacology, Insects, Kidneys, Malaria, Malpighian tubules, Malpighian Tubules - drug effects, Malpighian Tubules - metabolism, Malpighian Tubules - pathology, Medicine, Membrane Potentials - drug effects, Molecular Structure, Mosquitoes, Nervous system, Neurosciences, Patch-Clamp Techniques, Pathogens, Pharmacology, Physicians, Physiology, Potassium, Potassium - metabolism, Potassium Channel Blockers - chemistry, Potassium Channel Blockers - pharmacology, Potassium channels, Potassium channels (inwardly-rectifying), Potassium Channels, Inwardly Rectifying - antagonists & inhibitors, Potassium Channels, Inwardly Rectifying - genetics, Potassium Channels, Inwardly Rectifying - physiology, R&D, Renal failure, Research & development, Toxicity, Tropical diseases, Urine, Vector-borne diseases, Viral diseases