The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: Biochemical and pharmacological characterization

Milena Moretti, Michele Zoli, Andrew A. George, Ronald J. Lukas, Francesco Pistillo, Uwe Maskos, Paul Whiteaker, Cecilia Gotti

Research output: Contribution to journalArticle

Abstract

We examined α7β2-nicotinic acetylcholine receptor (α7β2-nAChR) expression in mammalian brain and compared pharmacological profiles of homomeric α7- nAChRs and α7β2-nAChRs. α-Bungarotoxin affinity purification or immunoprecipitation with anti-α7 subunit antibodies (Abs) was used to isolate nAChRs containing α7 subunits from mouse or human brain samples. α7β2-nAChRs were detected in forebrain, but not other tested regions, from both species, based on Western blot analysis of isolates using β2 subunit-specific Abs. Ab specificity was confirmed in control studies using subunit-null mutant mice or cell lines heterologously expressing specific human nAChR subtypes and subunits. Functional expression in Xenopus oocytes of concatenated pentameric (α7) 5-, (α7)42) 1-, and (α7)32) 2-nAChRs was confirmed using two-electrode voltage clamp recording of responses to nicotinic ligands. Importantly, pharmacological profiles were indistinguishable for concatenated (α7)5-nAChRs or for homomeric α7-nAChRs constituted from unlinked α7 subunits. Pharmacological profiles were similar for (α7)5-, (α7)42)1-, and (α7) 32)2-nAChRs except for diminished efficacy of nicotine (normalized to acetylcholine efficacy) at α7β2- versus α7-nAChRs. This study represents the first direct confirmation of α7β 2-nAChR expression in human and mouse forebrain, supporting previous mouse studies that suggested relevance of α7β2- nAChRs in Alzheimer disease etiopathogenesis. These data also indicate that α7β2-nAChR subunit isoforms with different α72 subunit ratios have similar pharmacological profiles to each other and to α7 homopentameric nAChRs. This supports the hypothesis that α7β 2-nAChR agonist activation predominantly or entirely reflects binding to α77 subunit interface sites.

Original languageEnglish
Pages (from-to)306-317
Number of pages12
JournalMolecular Pharmacology
Volume86
Issue number3
DOIs
Publication statusPublished - 2014

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Nicotinic Receptors
Pharmacology
Prosencephalon
Bungarotoxins
Antibodies
Brain
Xenopus
Nicotine
Immunoprecipitation
Acetylcholine
Oocytes
Alzheimer Disease
Electrodes
Protein Isoforms
Western Blotting
Ligands
Cell Line
Basal Forebrain

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain : Biochemical and pharmacological characterization. / Moretti, Milena; Zoli, Michele; George, Andrew A.; Lukas, Ronald J.; Pistillo, Francesco; Maskos, Uwe; Whiteaker, Paul; Gotti, Cecilia.

In: Molecular Pharmacology, Vol. 86, No. 3, 2014, p. 306-317.

Research output: Contribution to journalArticle

Moretti, Milena ; Zoli, Michele ; George, Andrew A. ; Lukas, Ronald J. ; Pistillo, Francesco ; Maskos, Uwe ; Whiteaker, Paul ; Gotti, Cecilia. / The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain : Biochemical and pharmacological characterization. In: Molecular Pharmacology. 2014 ; Vol. 86, No. 3. pp. 306-317.
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