Document Detail


Lack of cholinergic innervation in gastric mucosa does not affect gastrin secretion or basal acid output in neurturin receptor GFRα2 deficient mice.
MedLine Citation:
PMID:  23339174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Efferent signals from the vagus nerve are thought to mediate both basal and meal-induced gastric acid secretion, and provide trophic support of the mucosa. However, the underlying mechanisms are incompletely understood. Neurturin, signalling via glial cell line-derived neurotrophic factor (GDNF)-family receptor α2 (GFRα2), is essential for parasympathetic innervation of many target tissues but its role in gastric innervation is unknown. Here we show that most nerve fibres in wild-type mouse gastric mucosa, including all positive for gastrin-releasing peptide, are cholinergic. GFRα2-deficient (KO) mice lacked virtually all cholinergic nerve fibres and associated glial cells in the gastric (oxyntic and pyloric) mucosa but not in the smooth muscle, consistent with the selective expression of neurturin mRNA in the gastric mucosa. 2-Deoxyglucose and hexamethonium failed to affect acid secretion in the GFRα2-KO mice indicating the lack of functional innervation in gastric mucosa. Interestingly, basal and maximal histamine-induced acid secretion did not differ between wild-type and GFRα2-KO mice. Moreover, circulating gastrin levels in both fasted and fed animals, thickness of gastric mucosa, and density of parietal and different endocrine cells were similar. Carbachol-stimulated acid secretion was higher in GFRα2-KO mice, while atropine reduced basal secretion similarly in both genotypes. We conclude that cholinergic innervation of gastric mucosa depends on neurturin-GFRα2 signalling but is dispensable for gastrin secretion and for basal and maximal acid output. Basal acid secretion in the KO mice appears to be, at least partly, facilitated by constitutive activity of muscarinic receptors.
Authors:
Jussi Kupari; Jari Rossi; Karl-Heinz Herzig; Matti S Airaksinen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-21
Journal Detail:
Title:  The Journal of physiology     Volume:  591     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-16     Completed Date:  2013-10-18     Revised Date:  2014-04-15    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2175-88     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cholinergic Neurons / physiology
Female
Gastric Acid / secretion*
Gastric Mucosa / innervation*
Gastrins / blood,  secretion*
Glial Cell Line-Derived Neurotrophic Factor Receptors / physiology*
Hydrogen-Ion Concentration
Male
Mice
Mice, Knockout
Neuroglia / physiology
Neurturin / physiology
Chemical
Reg. No./Substance:
0/Gastrins; 0/Glial Cell Line-Derived Neurotrophic Factor Receptors; 0/Neurturin
Comments/Corrections

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