Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions

The aim of this study was to determine the functional role of muscarinic receptor subtypes regulating gallbladder cholinergic contractions. Electrical field stimulation (EFS; 16 Hz) produced contractile responses of guinea pig gallbladder muscle strips in vitro that were inhibited by 1 μM tetrodotoxin (2 ± 2% of control) and 1 μM atropine (1 ± 1% of control), indicating activation of intrinsic cholinergic nerves. Exogenous ACh (5 μM)-induced contractions were inhibited by atropine (1 ± 1% of control) but not tetrodotoxin (102 ± 1% of control), indicating a direct effect on smooth muscle. The M1 receptor antagonist pirenzepine (10 nM) had no effect on ACh-induced contractions but inhibited EFS-induced contractions by 11 ± 3%. The M2 antagonist methoctramine (10 nM) had no effect on ACh-induced contractions but augmented EFS-induced contractions by 5 ± 2%. The M3 antagonist 4-DAMP (10 nM) inhibited ACh-induced contractions by 14 ± 4% and EFS-induced contractions by 22 ± 5%. In conclusion, specific M1, M2, a...