The mode of action of neonicotinoids and related compounds on insect neuronal nicotinic acetylcholine receptors highlights complex intracellular calcium mechanisms
Steeve H. Thany
Abstract
Nicotinic acetylcholine receptors are ionotropic receptors which are widely expressed in the central nervous systems of insects. Activation of insect nicotinic acetylcholine receptors by neonicotinoids and related compounds induces an increase in intracellular calcium levels and thereby the activation of various intracellular calcium-dependent pathways. Nicotinic receptors are up- and down-regulated by different protein kinases, such as protein kinase A, C and G. Other kinases such as calcium calmodulin-dependent protein kinases (CaMKII) and CaMK kinase are also involved, leading to the release of calcium through the endoplasmic reticulum, or the dysfunction of mitochondrial activity. This complex intracellular mechanism influences nicotinic receptor function, and neonicotinoid pharmacology in several insect cells, such as the cockroach dorsal unpaired median neurosecretory cells. Most studies into the mode of action of neonicotinoid insecticides focus on toxicology, the role of metabolizing enzymes, and the characterization of the target receptors. This review exposes the importance of intracellular calcium pathways in the regulation of insect neuronal nicotinic acetylcholine receptors, and their role in the mode of action of neonicotinoid insecticides. We propose that these intracellular mechanisms could be essential for the development of more specific compounds in the future, and should therefore be studied further.