Open AccessEffect of genetic SSTR4 ablation on inflammatory peptide and receptor expression in the non‐inflamed and inflamed murine intestine
Author(s) -
Van Op den bosch Joeri,
Torfs Pascal,
De Winter Benedicte Y.,
De Man Joris G.,
Pelckmans Paul A.,
Van Marck Eric,
Grundy David,
Van Nassauw Luc,
Timmermans JeanPierre
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00760.x
Subject(s) - biology , somatostatin , neuropeptide , receptor , gene expression , inflammation , somatostatin receptor , microbiology and biotechnology , immunology , gene , endocrinology , genetics
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.