Identification of the nicotinic receptor subtypes expressed on dopaminergic terminals in the rat striatum.
Neuronal nicotinic acetylcholine receptors (nAChRs) expressed on mesostriatal dopaminergic neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Using immunoprecipitation and ligand-binding techniques, we have shown that both alpha6beta2* and alpha4(nonalpha6)beta2* nAChRs are expressed in the caudate-putamen and that only alpha6* nAChRs can bind alpha-conotoxin MII and methyllycaconitine with affinities of 1.3 and 40 nm, respectively. Further studies performed on 6-hydroxydopamine-lesioned striatum led to the identification of nAChR subtypes selectively expressed on dopaminergic terminals [alpha4alpha5beta2, alpha4alpha6beta2(beta3), and alpha6beta2(beta3)], nondopaminergic neuronal structures (alpha2alpha4beta2), or both structures (alpha4beta2). The identification of the nAChRs expressed on striatal dopaminergic terminals opens up the possibility of developing selective nAChR ligands active on dopaminergic systems and associated diseases, such as Parkinson's disease.
Zoli
Michele
M
Department of Biomedical Sciences, Section of Physiology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Moretti
Milena
M
Zanardi
Alessio
A
McIntosh
J Michael
JM
Clementi
Francesco
F
Gotti
Cecilia
C
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008024:Ligands; D008297:Male; D018722:Nicotinic Agonists / Q000493:pharmacokinetics; D018733:Nicotinic Antagonists / Q000493:pharmacokinetics; D016627:Oxidopamine; D011233:Precipitin Tests; D017729:Presynaptic Terminals / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000032:analysis / Q000096:biosynthesis* / Q000145:classification; D013047:Specific Pathogen-Free Organisms
D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D016627:Oxidopamine; D004298:Dopamine