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

38 Citations (Scopus)

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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