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

Abstract

To clarify the exact mechanisms of the pharmacological effects of glucagon on gastro intestinal motility, the following experiments were performed on the conscious and anesthe tized dogs. 1) During phase I of interdigestive migrating contractions (IMC) , glucagon (5 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 hex amethonium 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 contrac tions in any region. 3) Glucagon inhibited spontaneous phase III contractions and eryth romycin-induced phase III-like contractions in the antrum, but did not inhibit either contrac tions 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 inhib ited 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 con scious state.

Pharmacological Regulation of Postprandial Gastrointestinal Motility by Glucagon in Conscious Dogs.

“…Thus glucagon should inhibit postprandial motility in the intestine as well as in the antrum. In a previous report, I showed that glucagon enhanced cholinergic motor activities not in the antrum, but in the intestine, through preganglionic cholinergic neurons involving nicotinic and muscarinic receptors (Shimatani, 1997). Consequently, in the antrum glucagon inhibited postprandial motility through inhibition of gastrin release, but in the intestine glucagon-induced inhibitory responses might be reversed by glucagon-induced pregan glionic activation.…”

“…These results are shown in Fig. 5 by means (Shimatani, 1997). In order to examine the indirect effects of glucagon through hyperglycemia, glucose was used in place of glucagon, but did not affect postprandial motility in either region (Fig.…”

“…, 1975), and to interfere with intramural cholinergic neuronal transmission in rat esophagus (Lin et al, 1989). In a previous report I showed that glucagon inhibits cholinergic motor activities through postgang lionic cholinergic neurons in the antrum during the interdigestive state in dogs (Shimatani , 1997). Thus it is now thought that the enteric nervous system might be a target of glucagon.…”

“…In a previous report I demonstrated that glucagon inhibits cholinergic motor activities not directly, by binding to either receptor on the smooth muscle cells, but through postganglionic cholinergic neurons in the antrum during the interdigestive state (Shimatani, 1997).…”