Neuronal nicotinic receptors in the human brain

Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand gated ion channels which are widely distributed in the human brain. Multipl e subtypes of these receptors exist, each with individual pharmacological a nd functional profiles. They mediate the effects of nicotine, a widely used drug of abuse, are involved in a number of physiological and behavioural p rocesses and are additionally implicated in a number of pathological condit ions such as Alzheimer's disease, Parkinson's disease and schizophrenia. Th e nAChRs have a pentameric structure composed of five membrane spanning sub units, of which nine different types have thus far been identified and clon ed. The multiple subunits identified provide the basis for the heterogeneit y of structure and function observed in the nAChR subtypes and are responsi ble for the individual characteristics of each. A substantial amount of inf ormation on human nAChR structure and function has come from studies on neu roblastoma cell lines which naturally express nAChRs and from recombinant n AChRs expressed in Xenopus oocytes. In vitro brain nAChR distribution can b e mapped with a number of appropriate agonist and antagonist radioligands a nd subunit distribution may be mapped by in situ hybridization using subuni t specific mRNA probes. Receptor distribution in the living human brain can be studied with noninvasive imaging techniques such as PET and SPECT, with a significant reduction in nAChRs in the brains of Alzheimer's patients ha ving been identified with [C-11] nicotine in PET studies. Despite the signi ficant body of knowledge now accumulated about nAChRs, much remains to be e lucidated. This review will attempt to describe the current knowledge on th e nAChR subtypes in the human brain, their functional roles and neuropathol ogical involvement. (C) 2000 Elsevier Science Ltd. All rights reserved.