Aims: 

Efferent signals from the vagus nerve that converge on intrinsic neurons in the stomach wall mediate both basal and meal-induced gastric acid secretion. However, the development and the complex interplay of the neuronal, paracrine and hormonal mechanisms underlying gastric acid secretion are still incompletely understood. Neurturin, signaling via GDNF-family receptor 2 (GFR2), is essential for the target innervation of parasympathetic and a subset of enteric neurons but its role in stomach is unknown.

Methods: 

Gastric innervation was quantified using neuronal and glial markers in adult wild-type and GFR2-deficient (KO) mice. Basal and drug-stimulated gastric acid secretion was measured under urethane anesthesia using the acute gastric fistula method.

Results: 

GFR2-KO mice lacked most (>90%) of the intrinsic, efferent cholinergic nerve fibers and associated glial cells in the gastric mucosa but not in the smooth muscle, consistent with the selective expression of neurturin mRNA in the gastric mucosa. Surprisingly, gastric acid content and basal gastric acid secretion were similar between wild-type and GFR2-KO mice. Moreover, serum gastrin levels, thickness of gastric mucosa, number of parietal and D-cells, and maximal histamine-induced gastric acid secretion did not differ between the genotypes. Importantly, while gastric acid secretory response to vagal stimulation by 2-deoxyglucose was reduced, carbachol-induced acid secretion and serum ghrelin levels were increased in the GFR2-KO mice, presumably as a compensatory mechanism.

Conclusion: 

Our results show that the efferent innervation of the gastric mucosa depends on neurturin-GFR2 signaling but is not necessary for basal acid secretion. GFR2-KO mice provide a useful model to study neural regulation of gastric mucosal functions.