HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/G461    most recent 00424.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by McDonagh, S. C. Articles by Brubaker, P. L. Search for Related Content PubMed PubMed Citation Articles by McDonagh, S. C. Articles by Brubaker, P. L.

HORMONES AND SIGNALING

Role of glial cell-line derived neurotropic factor family receptor 2 in the actions of the glucagon-like peptides on the murine intestine

Departments of ¹Physiology and ²Medicine, University of Toronto, Toronto, Ontario, Canada

Submitted 13 September 2006 ; accepted in final form 12 June 2007

The intestinal glucagon-like peptides GLP-1 and GLP-2 inhibit intestinal motility, whereas GLP-2 also stimulates growth of the intestinal mucosa. However, the mechanisms of action of these peptides in the intestine remain poorly characterized. To determine the role of the enteric nervous system in the actions of GLP-1 and GLP-2 on the intestine, the glial cell line-derived neurotropic factor family receptor ₂ (GFR2) knockout (KO) mouse was employed. The mice exhibited decreased cholinergic staining, as well as reduced mRNA transcripts for substance P-ergic excitatory motoneurons in the enteric nervous system (ENS) (P < 0.05). Examination of parameters of intestinal growth (including small and large intestinal weight and small intestinal villus height, crypt depth, and crypt cell proliferation) demonstrated no differences between wild-type and KO mice in either basal or GLP-2-stimulated mucosal growth. Nonetheless, KO mice exhibited reduced numbers of synaptophysin-positive enteroendocrine cells (P < 0.05), as well as a markedly impaired basal gastrointestinal (GI) transit rate (P < 0.05). Furthermore, acute administration of GLP-1 and GLP-2 significantly inhibited transit rates in wild-type mice (P < 0.05–0.01) but had no effect in GFR2 KO mice. Despite these changes, expression of mRNA transcripts for the GLP receptors was not reduced in the ENS of KO animals, suggesting that GLP-1 and -2 modulate intestinal transit through enhancement of inhibitory input to cholinergic/substance P-ergic excitatory motoneurons. Together, these findings demonstrate a role for GFR2-expressing enteric neurons in the downstream signaling of the glucagon-like peptides to inhibit GI motility, but not in intestinal growth.

enteric nervous system; GFR2; GLP-1; GLP-2; growth; motility

This article has been cited by other articles:

				M. A. Brantley Jr, S. Jain, E. E. Barr, E. M. Johnson Jr, and J. Milbrandt Neurturin-Mediated Ret Activation Is Required for Retinal Function J. Neurosci., April 16, 2008; 28(16): 4123 - 4135. [Abstract] [Full Text] [PDF]