Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum.
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.
Grady
S R
SR
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309-0447, USA.
Meinerz
N M
NM
Cao
J
J
Reynolds
A M
AM
Picciotto
M R
MR
Changeux
J P
JP
McIntosh
J M
JM
Marks
M J
MJ
Collins
A C
AC
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
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