AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 4 732-G739, Copyright © 1992 by American Physiological Society
Calcitonin gene-related peptide: mechanisms of modulation of antral endocrine cells and cholinergic neurons
J. Ren, R. L. Young, D. C. Lassiter, M. C. Rings and R. F. Harty
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198.
Actions of human calcitonin-gene related peptide (hCGRP) on acetylcholine
(ACh) discharge and gastrin and somatostatin release from rat antral
mucosal-submucosal fragments were examined in both dynamic perifusion
experiments and short-term static incubation studies. The principal
findings of the dynamic perifusion experiments were that hCGRP exerted a
dual or biphasic effect on ACh discharge and gastrin release. Initial
exposure of antral tissues to hCGRP (1 x 10(-8) M) resulted in stimulation
of both ACh and gastrin release that was of brief duration. Continued hCGRP
perifusion caused subsequent inhibition of ACh and gastrin release that was
substantially greater in duration and magnitude than the initial
stimulatory responses. Static incubation studies indicated that hCGRP
(10(-10) to 10(-7) M) stimulated somatostatin and inhibited gastrin release
in a dose-dependent manner. Inhibition of gastrin and ACh release by hCGRP
appeared to be an indirect effect that was mediated by somatostatin as
suggested by studies with pertussis toxin (200 ng/ml). Furthermore, studies
with atropine (1 x 10(-6) M) and tetrodotoxin (1 x 10(-6) M) indicated that
CGRP-induced stimulation of somatostatin release and inhibition of ACh
discharge occurred independent of muscarinic receptor activation and nerve
excitation. In conclusion, results of these studies indicate that CGRP is
capable of exerting both stimulatory and inhibitory effects on ACh release
from mucosal-submucosal neurons and gastrin release from antral mucosal G
cells in in vitro studies. These data suggest that the inhibitory effects
of CGRP on cholinergic discharge and gastrin release are due to the
paracrine effects of somatostatin released from antral D cells by direct
action of CGRP.
