Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide

1990 ◽  
Vol 259 (6) ◽  
pp. G934-G939 ◽  
Author(s):  
M. W. Mulholland ◽  
S. Jaffer

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.

1992 ◽  
Vol 262 (4) ◽  
pp. G732-G739 ◽  
Author(s):  
J. Ren ◽  
R. L. Young ◽  
D. C. Lassiter ◽  
M. C. Rings ◽  
R. F. Harty

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.


1989 ◽  
Vol 256 (2) ◽  
pp. E331-E335 ◽  
Author(s):  
T. Chiba ◽  
A. Yamaguchi ◽  
T. Yamatani ◽  
A. Nakamura ◽  
T. Morishita ◽  
...  

From this study, we predicted that the human calcitonin gene-related peptide (hCGRP) fragment hCGRP-(8-37) would be a selective antagonist for CGRP receptors but an agonist for calcitonin (CT) receptors. In rat liver plasma membrane, where CGRP receptors predominate and CT appears to act through these receptors, hCGRP-(8-37) dose dependently displaced 125I-[Tyr0]rat CGRP binding. However, hCGRP-(8-37) had no effect on adenylate cyclase activity in liver plasma membrane. Furthermore, hCGRP-(8-37) inhibited adenylate cyclase activation induced not only by hCGRP but also by hCT. On the other hand, in LLC-PK1 cells, where calcitonin receptors are abundant and CGRP appears to act via these receptors, the bindings of 125I-[Tyr0]rat CGRP and 125I-hCT were both inhibited by hCGRP-(8-37). In contrast to liver membranes, interaction of hCGRP-(8-37) with these receptors led to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production in LLC-PK1 cells, and moreover, this fragment did not inhibit the increased production of cAMP induced not only by hCT but also by hCGRP. Thus hCGRP-(8-37) appears to be a useful tool for determining whether the action of CGRP as well as that of CT is mediated via specific CGRP receptors or CT receptors.


Cephalalgia ◽  
1993 ◽  
Vol 13 (3) ◽  
pp. 180-183 ◽  
Author(s):  
Richard D Piper ◽  
Lars Edvinsson ◽  
Rolf Ekman ◽  
Geoffrey A Lambert

There is circumstantial evidence that cortical spreading depression (SD) may account for the scotoma and the “spreading cortical oligemia” seen during migraine with aura. It has been shown that calcitonin gene-related peptide (CGRP) is increased in blood taken from the external jugular vein (EJV) in humans during migraine and after stimulation of the trigeminal ganglion. To test the hypothesis that cortical SD may elevate the concentration of this vasoactive peptide in the EJV during migraine, we have measured its concentration in the external jugular vein of cats during cortical SD. This study demonstrates that SD has no effect on the concentration of CGRP either during the passage of a wave of spreading depression across the cortex or, 60 min later, during the period of post-SD cortical oligemia.


2002 ◽  
Vol 123 (1-2) ◽  
pp. 83-90 ◽  
Author(s):  
Joseph P McGillis ◽  
Christopher N Miller ◽  
David B Schneider ◽  
Stefan Fernandez ◽  
Melissa Knopf

Neuroscience ◽  
1989 ◽  
Vol 30 (2) ◽  
pp. 503-513 ◽  
Author(s):  
P. Geppetti ◽  
E. Baldi ◽  
A. Castellucci ◽  
E. Del Bianco ◽  
P. Santicioli ◽  
...  

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