G-Protein-Coupled Receptors (GPCRs): An underdeveloped target for arthropod control

Aaron Gross is an Assistant Professor in the Department of Entomology (Virginia Tech). Originally from Minnesota, Aaron received his Bachelor of Science degrees in Biochemistry and Biomedical Sciences from St. Cloud State University. Graduate training was performed at Iowa State University of Science and Technology with MS and Ph.D. degrees in Toxicology with minors in Neuroscience and Entomology; Drs. Joel Coats and Michael Kimber served as his graduate major professors. At ISU, Aaron received a U.S. Environmental Protection Agency (EPA) – Science To Achieve Results (STAR) fellowship to investigate molecular target in the southern cattle tick. Postdoctoral training was at the Emerging Pathogens Institute, University of Florida under the direction of Dr. Jeffrey Bloomquist. In 2016, Aaron was the recipient of the New Investigator Award in the Agrochemical Division (AGRO) of the American Chemical Society (ACS), and in 2020 received the AGRO Division Fellow Award (ACS). At Virginia Tech, Aaron is affiliated with the School of Neuroscience, Fralin Life Science Institute, Virginia Tech’s Center for Emerging Zoonotic and Vector-borne Pathogens, and the Virginia Tech Center for Drug Discovery. He teaches Insecticide Toxicology along with Insect Physiology and Molecular Biology. Aaron’s lab (Molecular Physiology and Toxicology Laboratory) focuses on controlling arthropod pests that have an impact on human health, animal health, and agriculture with the goal of helping growers, producers, and public/animal health officials make informed pest control decisions. Research interests includes understanding the molecular mechanisms that are involved in insecticide/acaricide resistance. The use of G-Protein-Coupled Receptors (GPCRs), GPCR-related pathways, and ion channels as targets for insecticide/acaricide development. His lab is also investigating the molecular mechanisms that are involved in the ability of ticks to evade the mammalian immune response during blood feeding.

Agrochemicals (insecticides and acaricides) reduce arthropod populations, and thereby play a vital role in the protection of the global food supply and lessen the disastrous effects of arthropod-vectored diseases to humans and animals. Implementation of resistance management strategies requires the rotation of different insecticidal modes of action, which is not possible for all pest situations. Therefore, there is a continuous need to find new modes of action that can be integrated into management programs or disrupt the impacts of resistance. G-Protein-Coupled Receptors (GPCRs) have played a vital role in pharmaceutical development, but their utility has not seen the same expansion in agrochemicals; notwithstanding the physiological importance of GPCRs in arthropods. Agrochemical development against the cholinergic system has resulted in several classes of pesticidal chemistry; however, the muscarinic acetylcholine receptor (mAChR), a GPCR, has not been successfully exploited. A recently developed pyrazole oxime displays resistance-breaking activity with a favorable mammalian toxicity profile. Toxicological, biochemical and electrophysiology analyses indicate this new chemistry exerts its insecticidal properties through the modulation of a pharmacologically unique mAChR in insects (mAChR-B). In addition to new chemistry, target-site synergism may provide another opportunity for insecticide/acaricide development. Agonism and antagonism of mAChRs can enhance the toxicity of the gamma-aminobutyric acid chloride channel (GABA A ) insecticides (viz. fipronil, lindane, and dieldrin). A similar effect was observed with propoxur, a carbamate insecticide (acetylcholinesterase inhibitor). Using extracellular electrophysiology, pilocarpine (a non-selective mAChR agonist) significantly decreases the inhibitory firing effect of GABA A and carbamate insecticides. Collectively, the insect muscarinic system is a viable target for the development of insecticide and synergists.

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