Invertebrate nicotinic acetylcholine receptors -Targets for chemicals and drugs important in agriculture, veterinary medicine and human health

Abstract

The sequencing of several nematode and insect genomes has accelerated our understanding of the molecular and functional diversity of gene family members and their functional roles. The nicotinic acetylcholine receptor (nAChR) gene families, members of which mediate fast synaptic transmission and serve as targets for human and anthelmintic drugs as well as insecticides, are of considerable interest. Genomes of the free—living nematode and genetic model organism, Caenorhabditis elegans as well as the parasitic nematode Brugia malayii have been sequenced. Following the sequencing of the genome of the fruitfly Drosophila melanogaster, genomes are now available for the malarial vector Anopheles gambiae, the stored agricultural products pest Tribolium castaneum, a species of considerable agricultural benefit, the honeybee Apis mellifera, and other insects. Some nematode nAChR families are among the largest nAChR families known with many subunit isoforms, whereas insect nAChR families are often more compact. However, alternative splicing and RNA editing can ensure an equally rich molecular diversity of insect nAChRs. Subunits making up the L-type nematode levamisole-sensitive nAChR and the N-type nicotine-sensitive nAChR have now been identified and functionally expressed. Imidacloprid-sensitive nAChRs have also been expressed using hybrid receptors containing insect a subunits. Such studies are enhancing the prospects of receptor target—based screening for new animal health drugs and agricultural products.