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

FEBS Letters

Jakubík, Jan¹  Bačáková, Lucie¹  El-Fakahany, Esam E.²  Tuček, Stanislav¹ 

[1] Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic;Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

关键词: Muscarinic receptor;    Receptor;    muscarinic;    Constitutive receptor activity;    Atropine;    Methylscopolamine;    CHO cell;    Cardiomyocyte;   

DOI  :  10.1016/0014-5793(95)01360-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown