Local, exendin-(9-39)-insensitive, site of action of GLP-1 in canine ileum.
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 N(G)-nitro-L-arginine. 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.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. edaniel@ualberta.ca
E E
EE
Daniel
M
M
Anvari
J E T
JE
Fox-Threlkeld
T J
TJ
McDonald
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004285:Dogs; D004351:Drug Resistance; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D005934:Glucagon / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D014018:Tissue Distribution
D010446:Peptide Fragments; D011498:Protein Precursors; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002211:Capsaicin