HUMAN NEURONAL NICOTINIC RECEPTORS

Nicotine is a very widely used drug of abuse, which exerts a number of neurovegetative, behavioural and psychological effects by interacting with neuronal nicotinic acetylcholine receptors (NAChRs). These recep tors are distributed widely in human brain and ganglia, and form a fam ily of ACh-gated ion channels of different subtypes, each of which has a specific pharmacology and physiology. As human NAChRs have been imp licated in a number of human central nervous system disorders (includi ng the neurodegenerative Alzheimer's disease, schizophrenia and epilep sy), they are suitable potential targets for rational drug therapy. Mu ch of our current knowledge about the structure and function of NAChRs comes from studies carried out in other species, such as rodents and chicks, and information concerning human nicotinic receptors is still incomplete and scattered in the literature. Nevertheless, it is alread y evident that there are a number of differences in the anatomical dis tribution, physiology, pharmacology, and expression regulation of cert ain subtypes between the nicotinic systems of humans and other species . This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining the mo lecular basis of their functional diversity viewed mainly from pharmac ological and biochemical perspectives. It will also summarize our curr ent knowledge concerning the structure and function of the NAChRs expr essed by other species, and the newly discovered drugs used to classif y their numerous subtypes. Finally, the role of NAChRs in behaviour an d pathology will be considered. (C) 1997 Elsevier Science Ltd.