Premium
Demonstration of functional M 3 ‐muscarinic receptors in ventricular cardiomyocytes of adult rats
Author(s) -
Pönicke Klaus,
HeinrothHoffmann Ingrid,
Brodde OttoErich
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704997
Subject(s) - carbachol , pirenzepine , muscarinic acetylcholine receptor , endocrinology , medicine , receptor , pertussis toxin , receptor antagonist , inositol phosphate , antagonist , chemistry , phospholipase c , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m1 , methoctramine , atropine , inositol , biology , g protein
Muscarinic receptors (M‐receptors) in the mammalian heart are predominantly of the M 2 ‐subtype. The aim of this study was to find out whether there might exist an additional myocardial non‐M 2 ‐receptor. For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced [ 3 H]‐inositol phosphate (IP) formation, and its inhibition by M‐receptor antagonists. Carbachol (10 −7 –10 −3 mol l −1 ) increased IP‐formation (maximal increase: 14±3% above basal, n =6). This increase was significantly enhanced by pretreatment with pertussis toxin (PTX, 250 ng ml −1 for 20 h): maximal increase was 31±5%, pEC 50 ‐value was 5.08±0.33 ( n =6). In PTX‐pretreated cardiomyocytes 100 μmol l −1 carbachol‐induced IP‐formation was inhibited by atropine (pK i ‐value: 8.89±0.10) and by the M 3 ‐receptor antagonist darifenacin (pK i ‐value: 8.67±0.23) but was not significantly affected by the M 1 ‐receptor antagonist pirenzepine (1 μmol l −1 ) or the M 2 ‐receptor antagonists AF‐DX 116 and himbacine (1 μmol l −1 ). In conclusion, in adult rat cardiomyocytes there exists an additional, non‐M 2 ‐receptor, that is coupled to activation of the phospholipase C/IP 3 ‐pathway; this receptor is very likely of the M 3 ‐subtype.British Journal of Pharmacology (2003) 138 , 156–160. doi: 10.1038/sj.bjp.0704997