Constitutive activity of the M1-M4 subtypes of muscarinic receptors in transfected CHO cells and of muscarinic receptors in the heart cells revealed by negative antagonists
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Grant support
1 RO3 TW0017101
FIC NIH HHS - United States
A711103
PHS HHS - United States
PubMed
8543067
DOI
10.1016/0014-5793(95)01360-1
PII: 0014-5793(95)01360-1
Knihovny.cz E-resources
- MeSH
- Cyclic AMP biosynthesis MeSH
- Muscarinic Antagonists pharmacology MeSH
- Atropine pharmacology MeSH
- Quinuclidinyl Benzilate pharmacology MeSH
- CHO Cells MeSH
- Inositol Phosphates metabolism MeSH
- Carbachol pharmacology MeSH
- Cricetinae MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Myocardium cytology metabolism MeSH
- N-Methylscopolamine MeSH
- Pirenzepine analogs & derivatives pharmacology MeSH
- Receptors, Muscarinic drug effects genetics metabolism MeSH
- Scopolamine Derivatives pharmacology MeSH
- Transfection MeSH
- Tritium metabolism MeSH
- Animals MeSH
- Check Tag
- Cricetinae MeSH
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Names of Substances
- Cyclic AMP MeSH
- Muscarinic Antagonists MeSH
- Atropine MeSH
- Quinuclidinyl Benzilate MeSH
- Inositol Phosphates MeSH
- Carbachol MeSH
- N-Methylscopolamine MeSH
- otenzepad MeSH Browser
- Pirenzepine MeSH
- Receptors, Muscarinic MeSH
- Scopolamine Derivatives MeSH
- Tritium MeSH
We investigated whether muscarinic receptors of the M1-M4 receptor subtypes are constitutively active. We have found that the synthesis of cyclic AMP was enhanced by the muscarinic antagonists atropine and N-methylscopolamine (NMS) in Chinese hamster ovary (CHO) cells stably transfected with human m2 and m4 muscarinic receptor genes and in rat cardiomyocytes expressing the M2 receptor subtype, and that the production of inositol phosphates was inhibited by atropine and NMS in CHO cells stably transfected with human m1 and m3 and with rat m1 muscarinic receptor genes. The muscarinic antagonists quinuclidinyl benzilate and AF-DX 116 had no effect in some cases and acted like atropine and NMS in others. We conclude that the M1-M4 subtypes of muscarinic receptors are constitutively active in the CHO cell lines expressing them and in cardiomyocytes and that atropine and NMS act as negative antagonists on these receptor subtypes by stabilizing them in the inactive conformation.
References provided by Crossref.org
Divergence of allosteric effects of rapacuronium on binding and function of muscarinic receptors
Activation of muscarinic acetylcholine receptors via their allosteric binding sites
