Calcitonin gene-related peptide modulates acid-mediated regulation of somatostatin and gastrin release from rat antrum.
OBJECTIVE
Acid has been shown to stimulate calcitonin gene-related peptide (CGRP) release from peripheral sensory afferent nerve endings in the stomach. The aim of this study was to determine whether endogenous CGRP was involved, by a neurocrine mechanism, in acid-mediated stimulation of somatostatin and inhibition of gastrin release.


METHODS
A two-compartment sleeve of antral mucosal/submucosal tissue was perfused to determine sensory nerve and endocrine cell responses to luminal acid. CGRP receptor antagonist, CGRP8-37, was used to inhibit the actions of endogenously released CGRP.


RESULTS
Perfusion of the antral sleeve lumen with media of increasing hydrogen ion concentration caused pH-dependent increases in CGRP and somatostatin release and decrease in gastrin release. CGRP8-37 inhibited significantly basal somatostatin (-36%) and stimulated basal gastrin (+65%) release (P < 0.02). Furthermore, CGRP8-37 administration prevented luminal acid-mediated inhibition of gastrin release and stimulation of somatostatin release. These results indicate that CGRP8-37 prevented acid-mediated feedback inhibition of gastrin release and acid-induced feedforward somatostatin release.


CONCLUSIONS
These results suggest that CGRP plays an important role in the response of antral D and G cells to luminal acid and that local effector action of endogenous CGRP participates in regulation of antral regulatory peptide secretion.
Manela
F D
FD
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Ren
J
J
Gao
J
J
McGuigan
J E
JE
Harty
R F
RF
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D005744:Gastric Acid / Q000502:physiology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism*
D005755:Gastrins; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide