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

Jan Jakubík, Lucie Bačáková, Esam E. El-Fakahany, Stanislav Tuček

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72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)275-279
Number of pages5
JournalFEBS Letters
Volume377
Issue number2
DOIs
StatePublished - Dec 18 1995

Bibliographical note

Funding Information:
A 'knowledgements: This study was supported by Grant A711103 of the G "ant Agency of the Academy of Sciences of the Czech Republic and b NIH FIRC Award 1 RO3 TW0017101. We thank Drs. T.I. Bonner a~ d M. Brann for the CHO cell lines expressing the human muscarinic receptor genes, S.Z. Zhu for his share of work on the CHO cell lines expressing the rat ml receptor gene, and V. Lis/t for the preparation of cardiomyocytes.

Keywords

  • Atropine
  • CHO cell
  • Cardiomyocyte
  • Constitutive receptor activity
  • Methylscopolamine
  • Muscarinic receptor
  • Receptor, muscarinic

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