The increasing occurrence of insecticide resistance results in the need to identify new methods, chemistry, and targets for insect control. One greatly underutilized target class with diverse physiological functions is G-Protein-Coupled Receptors (GPCRs). Currently, a single insecticide/acaricide chemical, amitraz, is available on the market, which belongs to the formamidine insecticides/acaricides that activate octopamine receptors. The insect cholinergic system has long been a fruitful target for the development of insecticides that affect acetylcholinesterase or the nicotinic acetylcholine receptor. However, the muscarinic acetylcholine receptors (mAChRs), which are GPCRs, have not been successfully exploited as a target for agrochemicals to date, even though attempts have been made. Previously, it was reported that the muscarinic agonists block octopamine-stimulated cyclic adenosine monophosphate (cAMP) indicating a convergence of the two signal transduction pathways. We investigated this convergence using extracellular recordings from transected <i>Drosophila melanogaster</i> larval central nervous system (CNS) was used to investigate the electrogenesis and pharmacology of the octopaminergic and muscarinic systems.  Octopamine (10 µM) resulted in a sustained neuroexcitation during a 30 min exposure, and neuroexcitation after 21 min was blocked by the octopamine receptor antagonist, phentolamine (100 µM).  Exposure of this preparation to the non-selective mAChR agonist, pilocarpine (10 µM), resulted in a biphasic response, characterized by neuroexcitation followed by a decrease in the CNS firing rate below initial baseline levels.  This biphasic effect was antagonized by the classical mAChR antagonist atropine (10 µM).  It was also found that atropine (10 µM) blocked octopamine’s sustained neuroexcitation, indicating the possibility of cross-talk between these two GPCR pathways. Increasing our understanding of GPCRs and their signal transduction pathways could lead to the development of novel strategies to control insects.

Convergence of the octopaminergic and muscarinic signal transduction pathways in <i>Drosophila melanogaster</i>

2019 Fall National Meeting

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Convergence of the octopaminergic and muscarinic signal transduction pathways in Drosophila melanogaster