Neurosci Lett 2005 Sep 09;3852:168-72. doi: 10.1016/j.neulet.2005.05.014.

Insect-vertebrate chimeric nicotinic acetylcholine receptors identify a region, loop B to the N-terminus of the Drosophila Dalpha2 subunit, which contributes to neonicotinoid sensitivity.

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A chimera based on the chicken alpha4 nicotinic acetylcholine receptor (nAChR) subunit containing an insert from loop B to the N-terminus of the Drosophila melanogaster Dalpha2 (=SAD) subunit was constructed and co-expressed with the chicken beta2 nAChR subunit in Xenopus laevis oocytes. The actions of the neonicotinoid insecticide imidacloprid were examined. Replacement of the region loop B to the N-terminus of the alpha4 subunit by the corresponding region of the Dalpha2 subunit had little effect on the concentration-response curve for imidacloprid. However, replacement of Glu219 by proline in the YXCC motif in loop C of the chimeric alpha4 subunit resulted in a marked displacement to the left of the concentration-response curve for imidacloprid not seen when an equivalent mutation was made in the alpha4beta2 nAChR. The results suggest that the region loop B to the N-terminus in the Dalpha2 subunit contributes to the high imidacloprid sensitivity of the hybrid Dalpha2beta2 nAChR.

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