Emerging Pharmacological Properties of Cholinergic Synaptic Transmission: Comparison between Mammalian and Insect Synaptic and Extrasynaptic Nicotinic Receptors

Acetylcholine (ACh) is probably the oldest signalling neurotransmitter which appeared in evolution before the nervous system. It is present in bacteria, algae, protozoa and plants. In insects and mammals it is involved in cell-to-cell communications in various neuronal and non-neuronal tissues. The discovery of nicotinic acetylcholine receptors (nAChRs) as the main receptors involved in rapid cholinergic neurotransmission has helped to understand the role of ACh at synaptic level. Recently, several lines of evidence have indicated that extrasynaptically expressed nAChRs display distinct pharmacological properties from the ones expressed at synaptic level. The role of both nAChRs at insect extrasynaptic and/or synaptic levels has been underestimated due to the lack of pharmacological tools to identify different nicotinic receptor subtypes. In the present review, we summarize recent electrophysiological and pharmacological studies on the extrasynaptic and synaptic differences between insect and mammalian nAChR subtypes and we discuss on the pharmacological impact of several drugs such as neonicotinoid insecticides targeting these receptors. In fact, nAChRs are involved in a wide range of pathophysiological processes such as epilepsy, pain and a wide range of neurodegenerative and psychiatric disorders. In addition, they are the target sites of neonicotinoid insecticides which are known to act as nicotinic agonists causing severe poisoning in insects and mammals.