A Review on the Receptor-ligand Molecular Interactions in the Nicotinic Receptor Signaling Systems

Nicotine is regarded as the main active addictive ingredient in tobacco products driving continued tobacco abuse behavior (smoking) to the addiction behavior, whereas nicotinic acetylcholine receptors (nAChR) is the crucial effective apparatus or molecular effector of nicotine and acetylcholine and other similar ligands. Many nAChR subunits have been revealed to bind to either neurotransmitters or exogenous ligands, such as nicotine and acetylcholine, being involved in the nicotinic receptor signal transduction. Therefore, the nicotinic receptor signalling molecules and the receptor-ligand molecular interactions between nAChRs and their ligands are universally regarded as crucial mediators of cellular functions and drug targets in medical treatment and clinical diagnosis. Given numerous endeavours have been made in defining the roles of nAChRs in response to nicotine and other addictive drugs, this review focuses on studies and reports in recent years on the receptor-ligand interactions between nAChR receptors and ligands, including lipid-nAChR and protein-nAChR molecular interactions, relevant signal transduction pathways and their molecular mechanisms in the nicotinic receptor signalling systems. All the references were carefully retrieved from the PubMed database by searching key words "nicotine", "acetylcholine", "nicotinic acetylcholine receptor(s)", "nAChR*", "protein and nAChR", "lipid and nAChR", "smok*" and "tobacco". All the relevant referred papers and reports retrieved were fully reviewed for manual inspection. This effort intend to get a quick insight and understanding of the nicotinic receptor signalling and their molecular interactions mechanisms. Understanding the cellular receptor-ligand interactions and molecular mechanisms between nAChRs and ligands will lead to a better translational and therapeutic operations and outcomes for the prevention and treatment of nicotine addiction and other chronic drug addictions in the brain's reward circuitry.