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Am J Physiol Gastrointest Liver Physiol (May 15, 2002). doi:10.1152/ajpgi.00110.2002
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Articles in PresS, published online ahead of print May 15, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00110.2002
Submitted on March 20, 2002
Accepted on May 8, 2002

A Local, Exendin 9-39-Insensitive, Site of Action of GLP-1 in Canine Ileum

Edwin E Daniel1*, Mehran Anvari2, J. E. T. Fox-Threlkeld3, and Thomas J McDonald4

1 Department of Medicine, McMaster University, Hamilton, Ontario, Canada
2 Department of Surgery, McMaster University, Hamilton, Ontario, Canada
3 School of Nursing, McMaster University, Hamilton, Ontario, Canada
4 Department of Medicine, University of Western Ontario, London, Ontario, Canada

* To whom correspondence should be addressed. E-mail: edaniel{at}ualberta.ca.

GLP-1modulates 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 i.a. 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 sub-serosal 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 L-NOARG. Exendin 9-39, 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.




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