John Daly's compound, epibatidine, facilitates identification of nicotinic receptor subtypes.
The diversity of nicotinic acetylcholine receptor (nAChR) subtypes was explored by measuring the effects of gene deletion and pharmacological diversity of epibatidine binding sites in mouse brain. All epibatidine binding sites require expression of either the alpha7, beta2, or beta4 subunit. In agreement with general belief, the alpha4beta2*-nAChR and alpha7-nAChR subtypes are major components of the epibatidine binding sites. alpha4beta2*-nAChR sites account for approximately 70% of total high- and low-affinity epibatidine binding sites, while alpha7-nAChR accounts for 16% of the total sites all of which have lower affinity for epibatidine. The other subtypes are structurally diverse. Although these minor subtypes account for only 14% of total binding in whole brain, they are expressed at relatively high concentrations in specific brain areas indicating unique functional roles.
Marks
Michael J
MJ
Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA. Michael.Marks@Colorado.EDU
Laverty
Duncan S
DS
Whiteaker
Paul
P
Salminen
Outi
O
Grady
Sharon R
SR
McIntosh
J Michael
JM
Collins
Allan C
AC
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018722:Nicotinic Agonists / Q000494:pharmacology*; D021122:Protein Subunits / Q000032:analysis / Q000145:classification / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000032:analysis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
D019086:Bridged Bicyclo Compounds, Heterocyclic; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D021122:Protein Subunits; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C082748:epibatidine