Nicotinic cholinergic receptors in the rat cerebellum: multiple heteromeric subtypes

J Neurosci. 2005 Oct 5;25(40):9258-65. doi: 10.1523/JNEUROSCI.2112-05.2005.

Abstract

Nicotinic receptors (nAChRs) in the cerebellum have been implicated in the pathology of autism spectrum disorders (Lee et al., 2002; Martin-Ruiz et al., 2004). The subtypes of nAChRs in the cerebellum are not known in any detail, except that, in addition to the homomeric alpha7 subtype, there appears to be one or more heteromeric subtypes consisting of combinations of alpha and beta subunits. To begin to better understand the potential roles of these heteromeric nAChRs in cerebellar circuitry and their potential as targets for nicotinic drugs, we investigated their subunit composition. Using subunit-selective antibodies in sequential immunoprecipitation assays, we detected six structurally distinct heteromeric nAChR populations in the rat cerebellum. Among these were several subtypes that have not been encountered previously, including alpha3alpha4beta2 and alpha3alpha4beta4 nAChRs. This diversity suggests that nAChRs play multiple roles in cerebellar physiology.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Azetidines / pharmacokinetics
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Competitive Bidding / methods
  • Dose-Response Relationship, Drug
  • Immunoprecipitation / methods
  • Iodine Isotopes / pharmacokinetics
  • Nicotinic Agonists
  • Protein Binding / drug effects
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism*
  • Pyridines / pharmacokinetics
  • RNA, Messenger / metabolism
  • Radioligand Assay / methods
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic* / chemistry
  • Receptors, Nicotinic* / classification
  • Receptors, Nicotinic* / genetics
  • Receptors, Nicotinic* / metabolism
  • Tritium / pharmacokinetics

Substances

  • A 85380
  • Azetidines
  • Bridged Bicyclo Compounds, Heterocyclic
  • Iodine Isotopes
  • Nicotinic Agonists
  • Protein Subunits
  • Pyridines
  • RNA, Messenger
  • Receptors, Nicotinic
  • Tritium
  • epibatidine