The subunit composition and pharmacology of alpha-Conotoxin MII-binding nicotinic acetylcholine receptors studied by a novel membrane-binding assay

Neuropharmacology. 2005 Apr;48(5):696-705. doi: 10.1016/j.neuropharm.2004.12.011.


The subunit composition and pharmacology of alpha-Conotoxin MII-binding (alpha-CtxMII) nicotinic acetylcholine receptors (nAChR) was studied by an improved [(125)I]-alpha-CtxMII membrane binding method. This binding method facilitates pharmacological studies that have been difficult to accomplish with [(125)I]-alpha-CtxMII autoradiography or alpha-CtxMII inhibition of [(125)I]-epibatidine binding. Binding densities and K(d)-values obtained by this [(125)I]-alpha-CtxMII membrane binding were similar to the values obtained by autoradiography or alpha-CtxMII inhibition of [(125)I]-epibatidine binding, verifying that each of these approaches measures the same nAChR population. Binding results with nAChR subunit-null mutant mice confirm and extend observations from earlier studies: [(125)I]-alpha-CtxMII binding measures two sets of alpha6beta2* nAChR (alpha4alpha6beta2beta3 or alpha6beta2beta3). Most nicotinic agonists and antagonists show monophasic inhibition of [(125)I]-alpha-CtxMII binding, indicating that alpha4alpha6beta2beta3 and alpha6beta2beta3 have similar binding properties. Comparison of the binding and activation profiles of alpha6beta2* nAChR to those of other nAChR subtypes (alpha4beta2* and beta4*) indicates that these receptors have distinctly different pharmacology indicating that it may be possible to target alpha6beta2* nAChR selectively to develop compounds that might be therapeutically useful.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Alkaloids / pharmacology
  • Animals
  • Azetidines / pharmacology
  • Azocines / pharmacology
  • Binding, Competitive / drug effects
  • Brain / anatomy & histology
  • Brain / drug effects
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
  • Cell Membrane / drug effects*
  • Conotoxins / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Hydrogen-Ion Concentration
  • Iodine Isotopes / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacokinetics
  • Nicotinic Antagonists / pharmacology*
  • Protein Binding / drug effects
  • Protein Subunits / genetics
  • Pyridines / pharmacokinetics
  • Quinolizines / pharmacology
  • Radioligand Assay / methods
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / genetics
  • Time Factors


  • A 85380
  • Alkaloids
  • Azetidines
  • Azocines
  • Bridged Bicyclo Compounds, Heterocyclic
  • Conotoxins
  • Iodine Isotopes
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Protein Subunits
  • Pyridines
  • Quinolizines
  • Receptors, Nicotinic
  • alpha-conotoxin MII
  • cytisine
  • Nicotine
  • epibatidine
  • Acetylcholine