5‐Iodo‐A‐85380 binds to α‐conotoxin MII‐sensitive nicotinic acetylcholine receptors (nAChRs) as well as α4β2* subtypes

Publisher Website
Google Scholar
Abstract
Recent work suggests that 5-iodo-A-85380, a radioiodinated analog of the 3-pyridyl ether A-85380, represents a promising imaging agent for non-invasive, in vivo studies of α4β2* nicotinic acetylcholine receptors (nAChRs; *denotes receptors containing the indicated subunits), because of its low non-specific binding, low in vivo toxicity and high selectivity for α4β2* nAChRs. As an approach to elucidate nAChR subtypes expressed in striatum, we carried out competitive autoradiography in monkey and rat brain using 5-[125I]iodo-A-85380 ([125I]A-85380) and [125I]α-conotoxin MII, a ligand that binds with high affinity to α6* and α3* nAChRs, but not to α4β2* nAChRs. Although A-85380 is reported to be selective for α4β2* nAChRs, we observed that A-85380 completely inhibited [125I]α-conotoxin MII binding in rat striatum and that A-85380 blocked > 90% of [125I]α-conotoxin MII sites in monkey caudate and putamen. These results suggest that A-85380 binds to non-α4β2* nAChRs, including putative α6* nAChRs. Experiments to determine the percentage of [125I]A-85380 sites that contain α-conotoxin MII-sensitive (α6β2*) nAChRs indicate that they represent about 10% of [125I]A-85380 sites in rodent striatum and about 30% of sites in monkey caudate and putamen. These data are important for identifying alterations in nicotinic receptor subtypes in Parkinson's disease and other basal ganglia disorders both in in vitro and in in vivo imaging studies.