Vol. 283, Issue 3, G595-G602, September 2002
Local, exendin-(9
39)-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
