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Grady, SR, Meinerz, NM, Cao, J, Reynolds, AM, Picciotto, MR, Changeux, JP, McIntosh, JM, Marks, MJ and Collins, AC (2001) Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum. J. Neurochem. 76:258-68
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.
Acetylcholine/metabolism; Alkaloids/pharmacology; Animals; Azocines; Calcium/metabolism; Calcium/pharmacology; Choline/metabolism; Conotoxins/pharmacology; Corpus Striatum/metabolism; Dopamine/metabolism; Dose-Response Relationship, Drug; Female; Heterozygote; Homozygote; Male; Mesencephalon/drug effects; Mesencephalon/metabolism; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nicotinic Agonists/pharmacology; Nicotinic Antagonists/pharmacology; Presynaptic Terminals/metabolism; Protein Subunits; Quinolizines; Receptors, Nicotinic/genetics; Receptors, Nicotinic/metabolism; Synaptosomes/metabolism