Excitatory muscarinic M1 receptors mediate in the regulation of guinea-pig terminal ileum motility

In vitro experiments were performed on smooth muscle strips cut out longitudinally or circularly from the terminal ileum about 5 cm from the ileo-coecal sphincter. The aim of this study was to determine the functional role of M1 muscarinic receptor subtype in the regulation of cholinergic contractions of the guinea-pig terminal ileum. Electrical field stimulation (EFS; 16 Hz) produced in vitro contractile responses of the guinea-pig terminal ileum muscle strips (longitudinal and circular muscle layer). Those contractions were inhibited by 1 μM tetrodotoxin (2±2% of the control response) and 1 μM atropine (1±1% of the control response), thus indicating the activation of intrinsic cholinergic nerves. Exogenous ACh (1 μM) induced contractions that were inhibited by 1 μM atropine, but not by 1 μM tetrodotoxin, indicating a direct effect on the smooth muscle. MCN-343 specific agonist of M1 receptor subtype (5 μM) induced contractions that were inhibited by 1 μM atropine and by 1 μM tetrodotoxin. M1 receptor antagonist pirenzepine (10 nM) had no effect on ACh - induced contractions but reduced EFS - induced contractions by 11±3% and MCN-A-343 induced contractions by 17±4%. In conclusion, specific M1 receptors modulate terminal ileum contractions by regulating the release of ACh from cholinergic nerves. M1 receptors, present on cholinergic nerves, function as prejunctional facilitatory autoreceptors.