Roles of loop C and the loop B–C interval of the nicotinic receptor α subunit in its selective interactions with imidacloprid in insects

Shimomura, Masaru; Yokota, Maiko; Matsuda, Kazuhiko; Sattelle, David B.; Komai, Koichiro

doi:10.1016/j.neulet.2003.12.115

Cited by 68 publications

(55 citation statements)

References 13 publications

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“…5). Our earlier findings 21) and recent photoaffinity labeling experiments and homology modeling 22) indicated that the nitro group of neonicotinoids may interact with the X residue in the YXCC motif of loop C in the N terminal agonist binding domain of the a subunit. The a4 subunit has a glutamate residue as the X residue in loop C, which is predicted to result in electrostatic repulsion if it interacts directly with the nitro group.…”

Section: Discussionmentioning

confidence: 69%

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

et al. 2008

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Effects of imidacloprid, clothianidin, thiacloprid and related compounds on the acetylcholine (ACh)-induced response of the recombinant, expressed chicken a4b 2 nicotinic acetylcholine receptor (nAChR) were investigated using voltage-clamp electrophysiology. Imidacloprid and clothianidin enhanced the amplitude of the response to ACh of a4b 2 nAChR. In complete contrast, thiacloprid attenuated the amplitude of the response to ACh of a4b 2 nAChR. Replacing the nitro group of imidacloprid by a cyano group abolished the potentiating action, whereas exchanging the cyano group of thiacloprid for a nitro group conferred the ability to potentiate the ACh response. All three neonicotinoids shifted the ACh concentration-response curve without influencing the peak current amplitude of the ACh response.

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Section: Discussionmentioning

confidence: 69%

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

et al. 2008

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“…Interestingly, Ser-189 of AChBP corresponds to Glu in the vertebrate neuronal ␣4 and ␣7 nAChRs and faces inside the binding pocket based on the ␣4␤2 nAChR model (SI Fig. 11), whereas Val, Thr, Pro, Ala, or Ser takes its place in the insect ␣ subunits (20). The Glu negatively charged carboxyl residue possibly repels the electronegative nitro or cyano pharmacophore of the neonicotinoids in the vertebrate system.…”

Section: Discussion Some Common and Unique Molecular Aspects Of Neonimentioning

confidence: 99%

Mapping the elusive neonicotinoid binding site

Tomizawa

Talley

Maltby

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

115

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Two types of structurally similar nicotinic agonists have very different biological and physicochemical properties. Neonicotinoids, important insecticides including imidacloprid and thiacloprid, are nonprotonated and selective for insects and their nicotinic receptors, whereas nicotinoids such as nicotine and epibatidine are cationic and selective for mammalian systems. We discovered that a mollusk acetylcholine binding protein (AChBP), as a structural surrogate for the extracellular ligand-binding domain of the nicotinic receptor, is similarly sensitive to neonicotinoids and nicotinoids. It therefore seemed possible that the proposed very different interactions of the neonicotinoids and nicotinoids might be examined with a single AChBP by using optimized azidochloropyridinyl photoaffinity probes. Two azidoneonicotinoids with a nitro or cyano group were compared with the corresponding desnitro or descyano azidonicotinoids. acetylcholine binding protein ͉ imidacloprid ͉ neonicotinoid insecticides ͉ nicotinic receptor ͉ photoaffinity labeling S elective toxicity is critical for insecticide use, combining outstanding effectiveness for pests with safety for humans and wildlife. Neonicotinoids, exemplified by the major imidacloprid (IMI), thiacloprid (THIA), and acetamiprid (ACE) (Figs. 1 and 2), are the most important new class of insecticides of the past three decades and are increasingly replacing the organophosphates and methylcarbamates. The favorable selectivity of the neonicotinoids occurs largely at the target level, which is the agonist binding site of the nicotinic acetylcholine (ACh) receptor (nAChR). Nicotine, the namesake of the nAChR, has been used for pest control since the 17th century despite the risk for people and limited insecticidal efficacy. In contrast, the new and nicotine-like neonicotinoids have low activity on mammalian relative to insect nAChRs, providing a mechanistic basis for their safety (1, 2).Primary insights into the structure and function of agonistgated ion channel complexes came from electron microscopy analysis of the Torpedo nAChR (3) and x-ray crystallography of ACh binding proteins (AChBPs), soluble homologues of the nAChR extracellular drug-binding domain (4-7). Nicotine and its more potent analog epibatidine (EPI) (Fig. 2) (8) played a major role in structural characterization of the agonist-binding domain. Protonation of these agonists at physiological pH is important for binding site interactions at the superfamily of neurotransmitter-gated ion channels (5, 7, 9-11). Neonicotinoids, on the other hand, are uncharged with an electronegative nitro or cyano pharmacophore (12, 13). The first step in understanding neonicotinoid binding sites was identification of the molecular determinants for target site resistance and sitedirected mutagenesis (14-16), but such studies do not provide a complete description of the binding site.We report here that AChBP from the saltwater mollusk Aplysia californica surprisingly shows high sensitivity to the neonicotinoids. Photoaffinity labelin...

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Section: Neonicotinoids Contribute To Characterize Species Selectivitmentioning

confidence: 99%

“…The mutation of the Drosophila α 2 subunit proline (P243) to glutamate, equivalent to LsAChBP E163, was further found to decrease the sensitivity of the α 2 β 2 nAChR to imidacloprid [53]. Conversely, mutating the human α 4 subunit glutamate equivalent to LsAChBP E163 to a proline leads to an increase in sensitivity of the α 4 β 2 nAChR to imidacloprid [53]. Taking these data into account, it has been suggested that in heteromeric vertebrate nAChRs, the presence of acidic residues in the position equivalent to LsAChBP S186 would lead to electrostatic repulsion of acidic residues in the loop F on the complementary face.…”

Section: Neonicotinoids Contribute To Characterize Species Selectivitmentioning

confidence: 99%

Insight in nAChR subtype selectivity from AChBP crystal structures

Rucktooa

Smit²,

Sixma

2009

Biochemical Pharmacology

117

118

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Nicotinic acetylcholine receptors (nAChRs) display a broad variety of subtypes, which in turn present a complex subcellular and regional expression pattern in the brain, as well as a specific pharmacological profile. The association of these nAChRs with different types of brain disease has turned them into interesting drug targets for the treatment of Alzheimer's disease or schizophrenia, or for anti-smoking compounds among others. In the same way, muscle-type nAChRs present at neuromuscular junctions are also being targeted by muscle relaxants. However, to date no high-resolution structural data is available on functional

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Roles of loop C and the loop B–C interval of the nicotinic receptor α subunit in its selective interactions with imidacloprid in insects

Cited by 68 publications

References 13 publications

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

Mapping the elusive neonicotinoid binding site

Insight in nAChR subtype selectivity from AChBP crystal structures

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