Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum

J Neurochem. 2001 Jan;76(1):258-68. doi: 10.1046/j.1471-4159.2001.00019.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • Alkaloids
  • Azocines
  • Conotoxins
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Protein Subunits
  • Quinolizines
  • Receptors, Nicotinic
  • cytisine
  • Choline
  • Acetylcholine
  • Calcium
  • Dopamine