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Acta Physiologica 2008; Volume 193, Supplement 664
Scandinavian Physiological Society’s Annual Meeting 2008
8/15/2008-8/17/2008
Oulu, Finland
GFR2 KNOCKOUT MOUSE AS A MODEL FOR STUDYING AUTONOMIC REGULATION OF GASTRIC ACID AND GHRELIN SECRETION
Abstract number: P43
KUPARI1 J, ROSSI1 J, HUOTARI1 A, VOIKAR1 V, HERZIG1 K-H, AIRAKSINEN1 MS
1University of Helsinki, Neuroscience Center, Viikinkaari 4 Cultivator II, 00014 Helsingin yliopisto, Finland
GDNF-family receptor a2 (GFRa2) and its ligand neurturin are essential for cholinergic target innervation in parasympathetic and a subset of myenteric neurons. Here, we observed a deficit of 8090% of VIP and VAChT positive nerve fibers and associated glial cells in stomach mucosa in mice lacking GFRa2 (KO). Consistent with this, neurturin mRNA is expressed specifically in the basal part of the gastric mucosa in postnatal and adult mice. No difference in basal gastric pH (WT 2.20.37, KO 2.30.25) or gastric acid content (WT 0.240.02 mmol H+/g, KO 0.250.03 mmol H+/g) was seen between the phenotypes. However, vagal stimulation with 2-DG had little effect on KO acid secretion (~2 fold increase) when compared to WT animals (~8 fold increase). Ghrelin is an orexigenic peptide hormone produced primarily in the basal part of stomach mucosa. Cholinergic innervation has been proposed to regulate ghrelin secretion but factors promoting innervation of ghrelin producing cells are poorly known. Plasma ghrelin levels in KO animals were ~40% higher when compared to WT. However, no difference in mRNA levels of ghrelin between the genotypes was seen, suggesting increased ghrelin secretion in KO animals. KO mice showed abnormal feeding behaviour: shorter meal intervals and longer total feeding time. After overnight fast, the time and number of meals needed to reach the first long meal interval were increased in KO mice, suggesting reduced satiety. Unexpectedly, the time needed to initiate feeding after food re-presentation was longer in KO animals. Taken together, our results indicate that cholinergic innervation of gastric mucosa requires GFRa2 signaling and that GFRa2-KO mice provide a useful model for studying autonomic neuronal regulation of gastric acid and ghrelin secretion.
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Acta Physiologica 2008; Volume 193, Supplement 664 :P43