5-Iodo-A-85380 binds to alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors (nAChRs) as well as alpha4beta2* subtypes.

Paper

5-Iodo-A-85380 binds to alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors (nAChRs) as well as alpha4beta2* subtypes.

Published 2002 · J. M. Kulak, J. Sum, J. Musachio

Journal of neurochemistry

Q1 SJR score

22

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0

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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 alphaAbeta2* 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 alpha4beta2* 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]alpha-conotoxin MII, a ligand that binds with high affinity to alpha6* and alpha3* nAChRs, but not to alpha4beta2* nAChRs. Although A-85380 is reported to be selective for alpha4beta2* nAChRs, we observed that A-85380 completely inhibited [125I]alpha-conotoxin MII binding in rat striatum and that A-85380 blocked >90% of [125I] alpha-conotoxin MII sites in monkey caudate and putamen. These results suggest that A-85380 binds to non-alpha4beta2* nAChRs, including putative alpha6* nAChRs. Experiments to determine the percentage of [125I]A-85380 sites that contain alpha-conotoxin MII-sensitive (alpha6beta2*) 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.

In Vitro Study

Study Snapshot

5-iodo-A-85380 is a promising imaging agent for studying alpha4beta2* nicotinic acetylcholine receptors, but also binds to non-alpha4beta2* subtypes, potentially aiding in identifying alterations

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

5-Iodo-A-85380 binds to alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors (nAChRs) as well as alpha4beta2* subtypes.

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References

Citations

Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice

5-iodo-A-85380 is a potent 2-selective nicotinic receptor agonist in mice, with effects mediated by 2 subunits and partial agonist activity on 4(3)2(2) and 6-containing subtypes.

Comparison of effects produced by nicotine and the α4β2-selective agonist 5-I-A-85380 on intracranial self-stimulation in rats.

Selective 42-selective nAChR agonists may have higher abuse potential than nicotine, as they mediate abuse-related rate-increasing effects in intracranial self-stimulation in rats.

Effects of Nicotinic Acetylcholine Receptor Agonists in Assays of Acute Pain-Stimulated and Pain-Depressed Behaviors in Rats

Nicotine and 5-I-A-85380 effectively alleviate pain-related behavioral depression in rats, but nonselective effects may contribute to apparent antinociception.

ABT‐089 and ABT‐894 reduce levodopa‐induced dyskinesias in a monkey model of Parkinson's disease

ABT-089 and ABT-894, both nicotinic acetylcholine receptor agonists, show potential in reducing levodopa-induced dyskinesias in Parkinson's disease patients.

Nicotine reduces established levodopa‐induced dyskinesias in a monkey model of Parkinson's disease

Nicotine treatment effectively reduces levodopa-induced dyskinesias in a monkey model of Parkinson's disease, with no evidence of tolerance or worsening of parkinsonism.