title: Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum.
abstract: Acetylcholine release stimulated by nicotinic agonists was measured as radioactivity released from perfused synaptosomes prepared from mouse interpeduncular nucleus (IPN) that had been loaded with [(3)H]choline. Agonist-stimulated release was dependent upon external calcium and over 90% of released radioactivity was acetylcholine. The release process was characterized by dose response curves for 13 agonists and inhibition curves for six antagonists. alpha-Conotoxin MII did not inhibit this release, while alpha-conotoxin AuIB inhibited 50% of agonist-stimulated release. Comparison of this process with [(3)H]dopamine release from mouse striatal synaptosomes indicated that different forms of nicotinic acetylcholine receptors (nAChRs) may mediate these processes. This was confirmed by assays using mice homozygous for the beta 2 subunit null mutation. The deletion of the beta 2 subunit had no effect on agonist-stimulated acetylcholine release, but abolished agonist-stimulated release of dopamine from striatal synaptosomes. Mice heterozygous for the beta 2 subunit null mutation showed decreased dopamine release evoked by L-nicotine with no apparent change in EC(50) value, as well as similar decreases in both transient and persistent phases of release with no changes in desensitization rates.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309-0447, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Grady
authors.forename: N M
authors.initials: NM
authors.lastname: Meinerz
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: A M
authors.initials: AM
authors.lastname: Reynolds
authors.forename: M R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: J P
authors.initials: JP
authors.lastname: Changeux
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
authors.forename: M J
authors.initials: MJ
authors.lastname: Marks
authors.forename: A C
authors.initials: AC
authors.lastname: Collins
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D020916:Conotoxins / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D021122:Protein Subunits; D011807:Quinolizines; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
chemical_list: D000109:Acetylcholine; D000470:Alkaloids; D001392:Azocines; D002118:Calcium; D002794:Choline; D020916:Conotoxins; D004298:Dopamine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids