title: Alpha-conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes.
abstract: Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) can induce the release of neurotransmitters such as dopamine and norepinephrine in the CNS. Accumulating evidence suggests that distinct nAChR subtypes are involved; however, it has been difficult to determine the subunit composition of these receptors, in part because of the lack of a sufficient variety of selective nAChR ligands. We present experimental data that at least two different nAChR complexes are involved in dopamine release, one of which has an alpha3/beta2 subunit interface. The recently discovered peptide alpha-conotoxin MII is a potent and selective inhibitor of rat nAChRs containing an interface formed by alpha3 and beta2 subunits. We used this peptide to examine nicotine-stimulated release of dopamine from rat striatal synaptosomes and of norepinephrine from hippocampal synaptosomes. MII (100 nM) blocks 34-49% of the nicotine-stimulated dopamine release, but not dopamine release evoked by elevated [K+]. Furthermore, two peptides structurally related to alpha-conotoxin MII, namely alpha-conotoxin MI (selective for alpha1beta1gammadelta nAChRs) and alpha-conotoxin ImI (selective for alpha7-containing nAChRs), have no effect on nicotine-stimulated dopamine release. The results indicate that one third to half of the dopamine release in the striatal preparation is mediated by nAChRs with an alpha3/beta2 subunit interface. In contrast, </=10% of nicotine-stimulated release of norepinephrine from hippocampal synaptosomes is modulated by nAChRs with alpha3/beta2 subunit interfaces.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah, 84112, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Kulak
authors.forename: T A
authors.initials: TA
authors.lastname: Nguyen
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D020916:Conotoxins; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects*; D014793:Visual Cortex / Q000187:drug effects*
chemical_list: D020916:Conotoxins; D008978:Mollusk Venoms; D010455:Peptides; C098872:alpha-conotoxin MII; D009538:Nicotine; D004298:Dopamine