Involvement of Cholinergic Motor Neurons in Pharmacological Regulation of Gastrointestinal Motility by Glucagon in Conscious Dogs

To clarify the exact mechanisms of the pharmacological effects of glucagon on gastro intestinal motility, the following experiments were performed on the conscious and anesthetized dogs. 1) During phase I of interdigestive migrating contractions (IMC), glucagon (5-50μg/kg, drip infusion for 5 minutes) induced phasic contractions in the duodenum, jejunum and ileum, but not in the antrum. These excitatory responses were also observed in the truncal vagotomized dogs. These contractions were abolished by atropine or hexamethonium in the conscious dogs, and also by tetrodotoxin in the anesthetized dogs. 2) Glucagon inhibited cisapride-induced contractions only in the antrum in the conscious dogs .After pre-treatment with hexamethonium, glucagon inhibited these contractions in the duodenum, jejunum and ileum as well as in the antrum. After pre-treatment with tetrodotoxin in the anesthetized dogs, glucagon did not affect acetylcholine-induced contractions in any region. 3) Glucagon inhibited spontaneous phase III contractions and erythromycin-induced phase III-like contractions in the antrum, but did not inhibit either contractions in the other regions in the conscious dogs. These paradoxical effects of glucagon between the antrum and intestine were similar to those involved in the blockade of 5-hydroxytryptamine 3 receptors. After pre-treatment with hexamethonium, glucagon inhibited these contractions in the duodenum, jejunum and ileum as well as in the antrum . In conclusion: 1) Glucagon latently inhibits cholinergic motor activities in the antrum and intestine not directly, by binding to either receptor on the smooth muscle cells, but through postganglionic cholinergic neurons and possibly through 5-hydroxytryptamine neurons. 2) On the other hand, in the intestine the reverse effects through preganglionic cholinergic neurons involving nicotinic and muscarinic receptors are more potent . 3) As a result, glucagon inhibits antral contractions and does not affect intestinal contractions in a conscious state.