Details

Autor(en) / Beteiligte

• Porter, Amy C
• Bymaster, Frank P
• DeLapp, Neil W
• Yamada, Masahisa
• Wess, Jürgen
• Hamilton, Susan E
• Nathanson, Neil M
• Felder, Christian C

Titel

M1 muscarinic receptor signaling in mouse hippocampus and cortex

Ist Teil von

• Brain research, 2002-07, Vol.944 (1), p.82-89

Ort / Verlag

London: Elsevier B.V

Erscheinungsjahr

2002

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• The five subtypes (M1–M5) of muscarinic acetylcholine receptors signal through Gαq or Gαi/Gαo. M1, M3 and M5 receptors couple through Gαq and function predominantly as postsynaptic receptors in the central nervous system. M1 and M3 receptors are localized to brain regions involved in cognition, such as hippocampus and cortex, but their relative contribution to function has been difficult to ascertain due to the lack of subtype specific ligands. A functional and genetic approach was used to identify the predominant muscarinic receptor subtype(s) mediating responses in mouse hippocampus and cortex, as well as the relative degree of spare muscarinic receptors in hippocampus. The nonselective muscarinic agonist oxotremorine-M stimulated Gαq/11-specific GTP-γ- 35S binding in a concentration dependent manner with a Hill slope near unity in wild type mouse hippocampus and cortex. Muscarinic receptor stimulated Gαq/11-specific GTP-γ- 35S binding was virtually abolished in both the hippocampus and cortex of M1 receptor knockout (KO) mice. In contrast, there was no loss of signaling in M3 receptor KO mice in either brain region. Muscarinic receptor reserve in wildtype mouse hippocampus was measured by Furchgott analysis after partial receptor alkylation with propylbenzylcholine mustard. Occupation of just 15% of the M1 receptors in mouse hippocampus was required for maximal efficacy of oxotremorine-M-stimulated GTP-γ- 35S binding indicating a substantial level of spare receptors. These findings support a role for the M1 receptor subtype as the primary Gαq/11-coupled muscarinic receptor in mouse hippocampus and cortex.