Unique insecticide specificity of human homomeric ρ1 GABAC receptor

Ratra, Gurpreet S.; Erkkila, Brian E.; Weiss, David S.; Casida, John E.

doi:10.1016/s0378-4274(01)00471-4

Cited by 26 publications

(16 citation statements)

References 19 publications

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“…41,42) Studies of the effects of fipronil on the behavior, synaptic excitability, and sleep patterns of SpragueDawley rats revealed that the insecticide induced minor excitability. 43) Fipronil-sulfone was found to be the major metabolite in mice and appears in the brain, liver, kidney, fat and feces.…”

Section: Mammalsmentioning

confidence: 99%

Environmental fate and toxicology of fipronil

Gunasekara¹,

Truong²,

et al. 2007

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Section: Mammalsmentioning

confidence: 99%

Environmental fate and toxicology of fipronil

Gunasekara¹,

Truong²,

et al. 2007

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“…Recombinant receptors help define the relationship between subunit composition and insecticide action. [3][4][5] (Table 1). The b3 homopentameric GABAR is readily expressed and functional.…”

Section: Human Gabar B3 Homopentamer Conserves the Pharmacological Prmentioning

confidence: 99%

Insecticide interactions with .GAMMA.-aminobutyric acid and nicotinic receptors: predictive aspects of structural models

Casida¹,

Tomizawa²

2008

J. Pestic. Sci.

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An insecticide binding site may be blocked by widely diverse chemicals, as with the g-aminobutyric acid receptor (GABAR), or accept only closely related compounds, as illustrated by the nicotinic acetylcholine (ACh) receptor (nAChR). The human GABAR b3-homopentamer resembles the insect receptor in sensitivity and specificity for noncompetitive antagonists (NCAs), prompting exhaustive site-directed mutagenesis (cysteine scanning), which pinpointed the critical active site as pore-facing residues Ala-2Ј, Thr-6Ј and Leu-9Ј and led to a binding site model which fits several classes of insecticidal NCAs. The nAChR agonist site was approached with an ACh binding protein (AChBP) by photoaffinity labeling and neonicotinoid docking. Chloropyridinyl chlorine contacts Ile-106/Met-116 and nitrogen is directed to Ile-118/Trp-147 via a solvent bridge(s). The guanidine/amidine plane undergoes p-stacking with Tyr-188, and the nitro/cyano pharmacophore interacts with Ser-189/Cys-190, thereby defining the binding pocket that models AChBP and possibly nAChR potency and selectivity.

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“…Although fipronil target glutamate-activated chloride channels present in insects, suggesting a selective action mechanism, it also targets GABAergic receptors present in humans and animals [15,16] Recent work of our research group shown that memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats.…”

Section: Introductionmentioning

confidence: 99%

Lactational Exposure to Fipronil Pesticide in Low Dose Impairs Memory in Rat Offspring

Montanha¹,

Machado²

2016

J Neurol Disord

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Perinatal exposure to pesticides has been associated with neurotoxic changes that may occur during offspring development. This work aimed to evaluate the memory behavior in young and adult offspring from Wistar rats exposed to fipronil in the lactational period. For this, pregnant rats were distributed into two groups (N = 15) constituted as follows: control (Ct) and exposed to fipronil (Fip). Fipronil (Topline®) was administrated to mothers topically, at dose of 1 mg/kg/day, from the 7-14th day of lactation. The offspring memory behavior was assessed using the new object recognition task (ORT) and eight-radial arm maze task (8-RAM). Additionally was quantified the activity of the acetylcholinesterase enzyme (AChE) and made histopathological analysis of brain tissue. Results show persistent decreased memory behavior in offspring exposed to fipronil during lactation period associated with altered AChE activity and morphological changes in the animal's brain tissue. It is concluded that lactational exposure to fipronil provoked damage to the central nervous system (CNS) including altered memory behavior with histopathological and biochemical changes.

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Unique insecticide specificity of human homomeric ρ1 GABAC receptor

Cited by 26 publications

References 19 publications

Environmental fate and toxicology of fipronil

Environmental fate and toxicology of fipronil

Insecticide interactions with .GAMMA.-aminobutyric acid and nicotinic receptors: predictive aspects of structural models

Lactational Exposure to Fipronil Pesticide in Low Dose Impairs Memory in Rat Offspring

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