Drosophila CG12796 encodes a novel muscarinic acetylcholine receptor

Abstract: Most currently used insecticides are neurotoxic chemicals that target a limited number of sites and insect cholinergic neurotransmission is the major target. Organophosphates and methylcarbamates are inhibitors of acetylcholinesterase to cause abnormal accumulation of acetylcholine (ACh) and neonicotinoids act as agonists of the nicotinic ACh receptor (nAChR), a ligand-gated cation channel. A potential target for insecticides development is the muscarinic ACh receptor (mAChR) which is a metabotropic G-protein-coupled receptor. Insect has A- and B-type mAChRs and the five mammalian mAChRs are close to the A-type. We have isolated a cDNA (CG12796) from the fruit fly, Drosophila melanogaster. After heterologous expression in Chinese hamster ovary K1 cells (CHO-K1), CG12796 can be activated by acetylcholine chloride (EC₅₀, 73.02 nM) and oxotremorine M (EC₅₀, 48.23 nM) to increase intracellular Ca²⁺ levels. The classical mAChR antagonists atropine and scopolamine N-butylbromide at 100 mM can completely block the Ach-induced responses. The orthologs of CG12796 can be found in some insect pests and vectors such as beetles and mosquitoes, but not in the genomes of honeybee or parasitoid wasps. We suggest that CG12796 represents the first recognized member of a novel mAChR class.

 

Keywords: mAChR, neurotransmitter, G protein-coupled receptor, pharmacology