Document Detail

Gastrin release: Antrum microdialysis reveals a complex neural control.
MedLine Citation:
PMID:  20085791     Owner:  NLM     Status:  MEDLINE    
We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes confounding systemic effects. Microdialysis probes were placed in the submucosa on either side of the antrum, 3 days before the experiments. The concentration of gastrin in the antral submucosal compartment was about 20 times higher than in the microdialysate and estimated to be 5-10 times higher than in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently in both serum and microdialysate. Food intake induced a 2- to 3-fold increase in serum gastrin, while gastrin in antral microdialysate increased 10- to 15-fold. In unilaterally vagotomized rats (fasted, 3 days post-op.), food evoked a prompt peak gastrin release followed by a gradual decline on the intact side. On the vagotomized side of the antrum, the peak response seemed to be reduced while the microdialysate gastrin concentration remained elevated. Thus, unilateral vagotomy surprisingly raised the integrated gastrin response to food on the denervated side compared to the intact side, indicating that vagotomy suppresses an inhibitory as well as a stimulating effect on the G cells. While local infusion of atropine was without effect, infusion of the neuronal blocker tetrodotoxin (TTX) (which had no effect on basal gastrin) virtually abolished the food-evoked gastrin response and lowered the high microdialysate gastrin concentration in omeprazole-treated rats by 65%. We conclude that activated gastrin release, unlike basal gastrin release, is highly dependent on a neural input: 1) Vagal excitation has a transient stimulating effect on the G cells. The transient nature of the response suggests that the vagus has not only a prompt stimulatory but also a slow inhibitory effect on gastrin release. 2) Although vagal denervation did not affect the gastrin response to anacidity, the TTX experiments revealed that both food-evoked and anacidity-evoked gastrin release depends on neural input.
P Ericsson; R Håkanson; J F Rehfeld; P Norlén
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-18
Journal Detail:
Title:  Regulatory peptides     Volume:  161     ISSN:  1873-1686     ISO Abbreviation:  Regul. Pept.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-30     Completed Date:  2010-07-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100479     Medline TA:  Regul Pept     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  22-32     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier B.V. All rights reserved.
Experimental and Clinical Pharmacology, Department of Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden.
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MeSH Terms
Anti-Ulcer Agents / pharmacology
Gastric Mucosa / drug effects,  innervation,  metabolism
Gastrins / metabolism*
Microdialysis / methods*
Omeprazole / pharmacology
Rats, Sprague-Dawley
Tetrodotoxin / pharmacology
Vagus Nerve / physiology*,  surgery
Reg. No./Substance:
0/Anti-Ulcer Agents; 0/Gastrins; 4368-28-9/Tetrodotoxin; 73590-58-6/Omeprazole

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