AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 6 934-G939, Copyright © 1990 by American Physiological Society
Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide
M. W. Mulholland and S. Jaffer
Department of Surgery, University of Michigan, Ann Arbor 48109-0331.
The effects of calcitonin gene-related peptide (CGRP) on acetylcholine
(ACh) release from myenteric plexus neurons in primary culture were
investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase
in [3H]ACh release. The ACh release caused by CGRP was significantly
inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was
increased more than threefold by preincubation with theophylline.
Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence
of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced
[3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium
or substance P but not by cholecystokinin octapeptide or forskolin. The
results demonstrate that CGRP cause release of ACh from guinea pig
myenteric plexus neurons and suggest that the peptide acts through an
adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves
neuronal calcium channels.
