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Constitutive activity of the M 1 –M 4 subtypes of muscarinic receptors in transfected CHO cells and of muscarinic receptors in the heart cells revealed by negative antagonists
Author(s) -
Jakubík Jan,
Bačáková Lucie,
El-Fakahany Esam E.,
Tuček Stanislav
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01360-1
Subject(s) - muscarinic acetylcholine receptor , chinese hamster ovary cell , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m1 , receptor , atropine , muscarinic acetylcholine receptor m5 , transfection , endocrinology , muscarinic acetylcholine receptor m4 , chemistry , quinuclidinyl benzilate , muscarine , biology , microbiology and biotechnology , medicine , cell culture , biochemistry , genetics
We investigated whether muscarinic receptors of the M 1 –M 4 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 M 2 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 M 1 –M 4 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.