AJP - Gastrointestinal and Liver Physiology, Vol 249, Issue 1 147-G151, Copyright © 1985 by American Physiological Society
Receptor for calcitonin gene-related peptide: binding to exocrine pancreas mediates biological actions
H. Seifert, P. Sawchenko, J. Chesnut, J. Rivier, W. Vale and S. J. Pandol
In the present study we demonstrate by immunohistochemical techniques that
calcitonin gene-related peptide (CGRP) is present in nerve terminals in the
islets of Langerhans. Furthermore, binding studies with 125I-CGRP indicate
that dispersed acini from guinea pig pancreas contain a single class of
high-affinity binding sites for CGRP with an apparent dissociation constant
of 18 nM. Vasoactive intestinal peptide (VIP), rat growth hormone-releasing
factor (rGRF), cholecystokinin octapeptide (CCK-OP), and bombesin do not
interact with these receptors. Interaction of CGRP with these receptors
leads to release of amylase from the acinar cells. Amylase release is half
maximal at 0.3 nM CGRP and maximal at 3 nM CGRP. Maximal amylase release
with CGRP is one-third of that observed with VIP. CGRP-induced amylase
release is dependent on theophylline in the incubation medium. CGRP
potentiates the amylase release stimulated by bombesin and CCK-OP but has
no effect on amylase release stimulated by VIP, rGRF, and natural glucagon.
CGRP stimulates a 25% increase in basal cellular cAMP. These results
indicate that guinea pig pancreatic acinar cells contain a novel receptor
for CGRP and that interaction of CGRP with this receptor leads to digestive
enzyme secretion through a cAMP-mediated pathway. The presence of CGRP in
the islets of Langerhans suggests a pathway for CGRP to reach the exocrine
pancreas through an insuloacinar portal system.
