The regulation of hippocampal nicotinic acetylcholine receptors (nAChRs) after a protracted treatment with selective or nonselective nAChR agonists

James Auta, Patrizia Longone, Alessandro Guidotti, Erminio Costa

Research output: Contribution to journalArticle

Abstract

In rats, 1 mg/kg twice daily for 10 d of nicotine, a nonselective agonist of nicotinic acetylcholine receptors (nAChRs), fails to change α4 and β2 nAChR subunit mRNA but significantly decreased α7 nAChR subunit mRNA and protein expression, which is associated with a 35-40% decrease in the number of 125I-α-Bgtx binding sites in hippocampus. In addition, this schedule of nicotine treatment produced a 40% increase in the number of high- (K(D) 1 nM), but decreased by 25% the number of low-affinity (K(D) 30 nM) binding sites for 3H-epibatidine in hippocampus. In contrast, repeated treatment with lobeline (2.7 mg/kg twice daily for 10 d), which selectively binds to high-affinity binding nAChRs, fails to change the expression of high- or low-affinity nAChRs. These data suggest that a simultaneous upregulation of high-affinity nAChRs and downregulation of low-affinity nAChRs is elicited by ligands that can bind to both low- and high-affinity nAChRs, but not by selective agonists of high-affinity nAChRs. One might infer that in hippocampus, high- and low-affinity nAChRs may be located in the same cells. When these two receptor types are stimulated simultaneously by nonselective ligands for high- and low-affinity nAChRs, they interact, bringing about an increase in binding site density of the high-affinity nAChRs.

Original languageEnglish
Pages (from-to)31-45
Number of pages15
JournalJournal of Molecular Neuroscience
Volume13
Issue number1-2
Publication statusPublished - 1999

Keywords

  • Hippocampus
  • NAChR
  • NAChr agonists
  • Nicotine
  • Protein expression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

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