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Am J Physiol Gastrointest Liver Physiol 283: G595-G602, 2002. First published May 15, 2002; doi:10.1152/ajpgi.00110.2002
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Vol. 283, Issue 3, G595-G602, September 2002

Local, exendin-(939)-insensitive, site of action of GLP-1 in canine ileum

E. E. Daniel1, M. Anvari2, J. E. T. Fox-Threlkeld3, and T. J. McDonald4

Departments of 1 Medicine and 2 Surgery and 3 School of Nursing, McMaster University, Hamilton, Ontario L8N 3Z5; and 4 Department of Medicine, University of Western Ontario, London, Ontario, Canada N6A SA5

Glucagon-like peptide-1 (GLP-1) modulates glucose levels following a meal, including by inhibition of gastric emptying and intestinal transport. Intra-arterial injection of GLP-1 into the gastric corpus, antrum, or pylorus of anesthetized dogs had no effect on the contractile activity of the resting or neurally activated stomach. GLP-1 injected intra-arterially inhibited intestinal segments when activated by enteric nerve stimulation but not by acetylcholine. Isolated ileum segments were perfused intra-arterially, instrumented with strain gauges to record circular muscle activity and with subserosal electrodes to stimulate enteric nerves. GLP-1 caused concentration-dependent inhibition of nerve-stimulated phasic but not tonic activity. This was absent during TTX-induced activity and partly prevented by NG-nitro-L-arginine. Exendin-(939), the GLP-1 antagonist, had no intrinsic activity and did not affect the actions of GLP-1. Capsaicin mimicked the effects of GLP-1 and may have reduced the effect of subsequent GLP-1. GLP-1 may mediate paracrine action on afferent nerves in the canine ileal mucosa using an unusual receptor.

gastric emptying; intestinal motility; capsaicin; afferent nerves; paracrine action


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