Effect of glucagon, glicentin, glucagon-like peptide-1 and -2 on interdigestive gastroduodenal motility in dogs with a vagally denervated gastric pouch.
BACKGROUND
We previously reported that inhibition of gastric motility and hypertrophy of the small intestinal mucosa were observed after ileo-jejunal transposition which induced hypersecretion of enteroglucagon. Our aim was to study the effect of four enteroglucagon-related peptides (glucagon, glucagon-like peptide (GLP)-1, -2 and glicentin) on gastroduodenal motility and their mechanisms of action.


METHODS
The effect of these four peptides on motilin-induced interdigestive contractions was studied in dogs with vagally denervated gastric pouches equipped with four strain gauge force transducers on the pouch, gastric body, antrum and duodenum. Whether or not nitric oxide synthase inhibitor or phentolamine and propranolol reverses the inhibitory effect of those peptides was also studied.


RESULTS
Glucagon inhibited contractions in the pouch and stomach but had no effect on duodenal contractility. GLP-1 inhibited contractions at all sites. GLP-2 inhibited contractions in the pouch but did not affect motility in the neurally intact gastroduodenum. Glicentin had no effect on contractions at any site. Pretreatment with either a nitric oxide synthase inhibitor or phentolamine and propranolol reversed the inhibitory effect of glucagon, GLP-1 and GLP-2 on contractions in the pouch, but did not alter the inhibitory effect of glucagon and GLP-1 on motility in the neurally intact stomach and duodenum.


CONCLUSIONS
These results suggest that the effects of four peptides on gastroduodenal motility differ, and changes occur in the enteric neural modulation of motor activity after chronic surgical extrinsic denervation.
Shibata
C
C
Dept. of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. cshibata@gonryo.med.tohoku.ac.jp
Naito
H
H
Jin
X L
XL
Ueno
T
T
Funayama
Y
Y
Fukushima
K
K
Hashimoto
A
A
Matsuno
S
S
Sasaki
I
I
D000818:Animals; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D053771:Glicentin; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000601:surgery; D014628:Vagotomy
D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D004763:Glucagon-Like Peptides; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon