Subunit Composition and Pharmacology of Two Classes of Striatal Presynaptic Nicotinic Acetylcholine Receptors Mediating Dopamine Release in Mice

• DOI: 10.1124/mol.65.6.1526
• Publication Date: 2004-05-21T03:38:08Z
• Authors: Outi Salminen; Karen L. Murphy; J. Michael McIntosh; John Drago; Michael J. Marks; Allan C. Collins; Sharon R. Grady
• Keywords: D2-like receptor

Pharmacological evaluation of nicotine-stimulated dopamine release from striatum has yielded data consistent with activation a single population nicotinic acetylcholine receptors (nAChR). However, discovery that α-conotoxin MII (α-CtxMII) partially inhibits the response indicates two classes presynaptic nAChRs mediate release. We have investigated pharmacology and subunit composition these nAChR. Inhibition mouse striatal synaptosomes by α-CtxMII occurs within minutes; recovery is slow. The IC₅₀ 1 to 3 nM. α-CtxMII-sensitive -resistant components significant differences in pharmacology. five agonists tested were more potent at activating nAChRs; indeed, this receptor highest affinity functional nAChR found, so far, brain. In addition, cytisine was efficacious sites. Methyllycaconitine 9-fold inhibiting sites, whereas dihydro-β-erythroidine 7-fold inhibitor α-CtxMII-resistant response. Both transient persistent phases inhibited equal potency. nAChRs, assessed mice null mutations for individual subunits. β2 an absolute requirement both classes. contrast, deletion β4 or α7 subunits had no effect. requires β3 dependent upon α4 subunits, probably α6β3β2 α4α6β3β2, α5 α4β2 α4α5β2.