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Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice

Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice

Authors :
Lu Zhang
Harlan E. Shannon
Evi Kostenis
Christian C. Felder
Hui Sheng
Alexander Grinberg
Jesus Gomeza
Jesse Brodkin
Jürgen Wess
Source :
Proceedings of the National Academy of Sciences. 96:1692-1697
Publication Year :
1999
Publisher :
Proceedings of the National Academy of Sciences, 1999.

Abstract

Members of the muscarinic acetylcholine receptor family (M1–M5) are known to be involved in a great number of important central and peripheral physiological and pathophysiological processes. Because of the overlapping expression patterns of the M1–M5 muscarinic receptor subtypes and the lack of ligands endowed with sufficient subtype selectivity, the precise physiological functions of the individual receptor subtypes remain to be elucidated. To explore the physiological roles of the M2 muscarinic receptor, we have generated mice lacking functional M2 receptors by using targeted mutagenesis in mouse embryonic stem cells. The resulting mutant mice were analyzed in several behavioral and pharmacologic tests. These studies showed that the M2 muscarinic receptor subtype, besides its well documented involvement in the regulation of heart rate, plays a key role in mediating muscarinic receptor-dependent movement and temperature control as well as antinociceptive responses, three of the most prominent central muscarinic effects. These results offer a rational basis for the development of novel muscarinic drugs.

Details

ISSN :
10916490 and 00278424
Volume :
96
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences
Accession number :
edsair.doi.dedup.....c419fcc4fa7af2da95e3b5a1e92a4d10
Full Text :
https://doi.org/10.1073/pnas.96.4.1692