Structural and functional diversity of native brain neuronal nicotinic receptors.
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels present in the central and peripheral nervous systems, that are permeable to mono- and divalent cations. They share a common basic structure but their pharmacological and functional properties arise from the wide range of different subunit combinations making up distinctive subtypes. nAChRs are involved in many physiological functions in the central and peripheral nervous systems, and are the targets of the widely used drug of abuse nicotine. In addition to tobacco dependence, changes in their number and/or function are associated with neuropsychiatric disorders, ranging from epilepsy to dementia. Although some of the neural circuits involved in the acute and chronic effects of nicotine have been identified, much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions. We briefly review some recent findings concerning the structure and function of native nAChRs, focusing on the subtypes identified in the mesostriatal and habenulo-interpeduncular pathways, two systems involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the effect of chronic nicotine on the expression of native subtypes.
Gotti
Cecilia
C
Department of Medical Pharmacology, CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology, University of Milan, Milan, Italy. c.gotti@in.cnr.it
Clementi
Francesco
F
Fornari
Alice
A
Gaimarri
Annalisa
A
Guiducci
Stefania
S
Manfredi
Irene
I
Moretti
Milena
M
Pedrazzi
Patrizia
P
Pucci
Luca
L
Zoli
Michele
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D014029:Tobacco Use Disorder / Q000378:metabolism / Q000503:physiopathology
D018722:Nicotinic Agonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D009538:Nicotine