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Mode of action of the plant-derived silphinenes on insect and mammalian GABA(A) receptor/chloride channel complex

AutorBloomquist, Jeffrey R.; Boina, Dhana Raj; Chow, Ella; Carlier, Paul R.; Reina, Matías ; González-Coloma, Azucena
Palabras claveGABA antagonist
Senecio palmensis
Fecha de publicaciónmay-2008
CitaciónPesticide Biochemistry and Physiology 91(1): 17-23 (2008)
ResumenThe silphinenes are tricyclic sesquiterpenes that have antifeedant and toxic effects in insects and structural similarity to the known GABA antagonist, picrotoxinin. In murine synaptoneurosomes, silphinenes block GABA-stimulated influx of Cl-36(−) with EC-50s in the range of 10–30 μM. In insects, silphinenes were tested in neurophysiological recordings of central neurons from third instar Drosophila melanogaster larvae. Silphinenes reversed the blockage of neuronal firing induced by GABA, but had little effect below 100 μM. The structure–activity profile observed in the murine chloride flux assay was also observed in the larval neurophysiological assay, indicating little selectivity for the silphinenes. A reference silphinene was equally active on nerve preparations from the rdl strain of D. melanogaster, which is resistant to channel-blocking antagonists via an altered GABA receptor. This latter finding suggests that silphinenes interact with the insect GABA receptor in a manner somewhat different from PTX, and that rdl resistance in the field may have little effect on silphinene efficacy.
Descripción7 pages, 6 figures, 1 table.-- Available online Dec 23, 2007.
Versión del editorhttp://dx.doi.org/10.1016/j.pestbp.2007.12.002
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