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Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice
Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice
- 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.
- Subjects :
- Multidisciplinary
Muscarinic acetylcholine receptor M3
Muscarinic acetylcholine receptor M2
Biological Sciences
Pharmacology
Biology
Knockout mouse
Muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor M5
Muscarinic acetylcholine receptor M4
Oxotremorine
medicine
Receptor
Neuroscience
medicine.drug
Subjects
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