Actions of picrodendrin antagonists on dieldrin‐sensitive and ‐resistant <i>Drosophila</i> GABA receptors

Hosie, Alastair M.; Ozoe, Yoshihisa; Koike, Kazuo; Ohmoto, Taichi; Nikaido, Tamotsu; Sattelle, David B.

doi:10.1111/j.1476-5381.1996.tb16074.x

Cited by 34 publications

(14 citation statements)

References 58 publications

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“…), the antagonistic action of which is also abolished by the TM2 mutation (Hosie et al . ). While the effects of pyrethroids on GABA responses were initially attributed to action on GABA receptors (Wakeling et al .…”

Section: Discussionmentioning

confidence: 97%

The neonicotinoid imidacloprid, and the pyrethroid deltamethrin, are antagonists of the insect Rdl GABA receptor

Taylor-Wells

Brooke

Bermúdez

et al. 2015

Journal of Neurochemistry

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A mutation in the second transmembrane domain of the GABA receptor subunit, Rdl, is associated with resistance to insecticides such as dieldrin and fipronil. Molecular cloning of Rdl cDNA from a strain of the malaria mosquito, Anopheles gambiae, which is highly resistant to dieldrin revealed this mutation (A296G) as well as another mutation in the third transmembrane domain (T345M). Wild-type, A296G, T345M and A296G + T345M homomultimeric Rdl were expressed in Xenopus laevis oocytes and their sensitivities to fipronil, deltamethrin, 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT), imidacloprid and spinosad were measured using twoelectrode voltage-clamp electrophysiology. Spinosad and DDT had no agonist or antagonist actions on Rdl. However, fipronil, deltamethrin and imidacloprid decreased GABAevoked currents. These antagonistic actions were either reduced or abolished with the A296G and the A296G + T345M mutations while T345M alone appeared to have no significant effect. In conclusion, this study identifies another mutation in the mosquito Rdl that is associated with insecticide resistance. While T345M itself does not affect insecticide sensitivity, it may serve to offset the structural impact of A296G. The present study also highlights Rdl as a potential secondary target for neonicotinoids and pyrethroids.

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Section: Discussionmentioning

confidence: 97%

The neonicotinoid imidacloprid, and the pyrethroid deltamethrin, are antagonists of the insect Rdl GABA receptor

Taylor-Wells

Brooke

Bermúdez

et al. 2015

Journal of Neurochemistry

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“…PTX was the first described chloride channel blocker, and other PTX-like natural products are structurally-related terpenoids, including the tutins and picrodendrins (Fig. 1) that are also isolated from plants (Hosie et al, 1996). The rank order of potency for picrodendrin displacement of EBOB binding in housefly membranes showed a better correlation with their PB-synergized toxicity to Blattella germanica by injection, than it did for blocking GABA-gated currents in expressed GABAgated homomultimeric receptors (Ozoe et al, 1998).…”

Section: Gaba Receptor As An Insecticide Targetmentioning

confidence: 99%

Chloride channels as tools for developing selective insecticides

Bloomquist

2003

Arch Insect Biochem Physiol

242

113

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Ligand-gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA-gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate-gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel-directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.The voltage-sensitive chloride channels form another large gene family of chloride channels. Voltage-dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for insecticide development.

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“…Many recombinant GluCls described to date are blocked by the convulsant picrotoxinin (PTX), a plant derived toxin that blocks vertebrate and invertebrate native and recombinant GABA‐ and glycine‐gated anion channels ( Cull‐Candy, 1976 ; Olsen & Tobin, 1990 ; Pribilla et al ., 1992 ; Hosie et al ., 1997 ). A number of convulsants also act at insect GABA‐gated anion channels, including PTX, the picrodendrins ( Hosie et al ., 1996 ), the bicyclic dinitrile BIDN ( Rauh et al ., 1997 ; Hamon et al ., 1998 ) as well as fipronil ( Cole et al ., 1993 ; Hosie et al ., 1995 ). The antagonist activity of these compounds is thought to target the convulsant binding sites of the Drosophila melanogaster GABA‐gated chloride channel subunit, RDL ( Shirai et al ., 1995 ; Hosie et al ., 1997 ).…”

Section: Introductionmentioning

confidence: 99%

GLC‐3: a novel fipronil and BIDN‐sensitive, but picrotoxinin‐insensitive, L‐glutamate‐gated chloride channel subunit from Caenorhabditis elegans

Horoszok

Raymond

Sattelle

et al. 2001

British J Pharmacology

112

101

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1 We report the cloning and expression of a novel Caenorhabditis elegans polypeptide, GLC-3, with high sequence identity to previously cloned L-glutamate-gated chloride channel subunits from nematodes and insects. 2 Expression of glc-3 cRNA in Xenopus oocytes resulted in the formation of homo-oligomeric Lglutamate-gated chloride channels with robust and rapidly desensitizing currents, an EC 50 of 1.9+0.03 mM and a Hill coecient of 1.5+0.1. GABA, glycine, histamine and NMDA all failed to activate the GLC-3 homo-oligomer at concentrations of 1 mM. The anthelminthic, ivermectin, directly and irreversibly activated the L-glutamate-gated channel with an EC 50 of 0.4+0.02 mM. 3 The GLC-3 channels were selective for chloride ions, as shown by the shift in the reversal potential for L-glutamate-gated currents after the reduction of external Cl 7 from 107.6 to 62.5 mM. 4 Picrotoxinin failed to inhibit L-glutamate agonist responses at concentrations up to 1 mM. The polycyclic dinitrile, 3,3-bis-tri¯uoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile (BIDN), completely blocked L-glutamate-induced chloride currents recorded from oocytes expressing GLC-3 with an IC 50 of 0.2+0.07 mM. The phenylpyrazole insecticide, ®pronil, reversibly inhibited L-glutamate-gated currents recorded from the GLC-3 receptor with an IC 50 of 11.5+0.11 mM. 5 In this study, we detail the unusual antagonist pharmacology of a new GluCl subunit from C. elegans. Unlike all other native and recombinant nematode GluCl reported to date, the GLC-3 receptor is insensitive to picrotoxinin, but is sensitive to two other channel blockers, BIDN and ®pronil. Further study of this receptor may provide insights into the molecular basis of noncompetitive antagonism by these compounds.

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Actions of picrodendrin antagonists on dieldrin‐sensitive and ‐resistant Drosophila GABA receptors

Cited by 34 publications

References 58 publications

The neonicotinoid imidacloprid, and the pyrethroid deltamethrin, are antagonists of the insect Rdl GABA receptor

The neonicotinoid imidacloprid, and the pyrethroid deltamethrin, are antagonists of the insect Rdl GABA receptor

Chloride channels as tools for developing selective insecticides

GLC‐3: a novel fipronil and BIDN‐sensitive, but picrotoxinin‐insensitive, L‐glutamate‐gated chloride channel subunit from Caenorhabditis elegans

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