Effect of genetic SSTR4 ablation on inflammatory peptide and receptor expression in the non-inflamed and inflamed murine intestine.
The recently suggested pivotal role of somatostatin (SOM) receptor 4 (SSTR4) in inflammation and nociception in several non-intestinal organs and in gastrointestinal (GI) physiology, necessitates exploration of the role of SSTR4 in GI pathophysiology. Therefore, the role of SSTR4 in GI activity was explored by investigating the effects of SSTR4 deficiency on intestinal motility, smooth muscle contractility and on the expression of SSTRs and neuropeptides in the healthy and Schistosoma mansoni-infected murine small intestine. Functional experiments revealed no differences in intestinal motility or smooth muscle cell contractility between wild-type and SSTR4 knockout (SSTR4(-/-)) mice in physiological conditions. As revealed by multiple immunofluorescent labellings, RT-PCR and quantitative real time RT-PCR (qPCR), genetic deficiency of SSTR4 considerably altered the expression of SOM and SSTRs in non-inflamed and inflamed conditions, affecting both extrinsic and intrinsic components of the intestinal innervation, along with SSTR expression in several non-neuronal cell types. Moreover, substance P and calcitonin gene-related peptide expression were significantly elevated in SSTR4(-/-) mice, confirming the modulatory role of SSTR4 on intestinal pro-inflammatory neuropeptide expression. These data suggest that SSTR4 plays a previously unexpected modulatory role in the regulation of intestinal SSTR expression. Moreover, in addition to the recently described inhibitory effects of SSTR4 on the neuronal release of pro-inflammatory peptides, SSTR4 appears also to be involved in the neuronal expression of both pro- and anti-inflammatory peptides in the murine small intestine.
Laboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerpen, Belgium.
Joeri
J
Van Op den Bosch
Pascal
P
Torfs
Benedicte Y
BY
De Winter
Joris G
JG
De Man
Paul A
PA
Pelckmans
Eric
E
Van Marck
David
D
Grundy
Luc
L
Van Nassauw
Jean-Pierre
JP
Timmermans
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000378:metabolism
D010455:Peptides; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide