Exogenous interleukin-6 facilitated the contraction of the colon in a depression rat model.

BACKGROUND: Gut dysmotility is closely associated with proinflammatory cytokines both in irritable bowel syndrome and inflammatory bowel disease. There is a dose-response relationship between depression and these inflammatory cytokines. AIMS: In the present study, we aimed to investigate the effect of Interleukin-6 (IL-6) on colon motility in a rat model of depression induced by chronic unpredictable mild stress (CUMS). METHODS: The contraction of the circular muscle strips of proximal colon was monitored by a polygraph. IL-6 and IL-6 receptor (IL-6R) mRNA was assayed by real-time quantitative PCR. Immunohistochemistry staining was used to locate the IL-6 and IL-6R in the rat colon. RESULTS: IL-6 and IL-6R were expressed in the mucosal layer, smooth muscle cells, and myenteric plexus of the colon. Exogenous IL-6 (20 ng/ml) increased the contraction of the circular muscle strip. Pretreatment of tetrodotoxin (blocker of voltage-dependent Na(+) channel on nerve fiber) blocks the excitatory effect of IL-6 on the contraction of the colon in non-stressed rats, but partially inhibited IL-6-induced excitatory effect on the muscle strips in CUMS-treated rats. CONCLUSIONS: These results suggest that IL-6-induced the contraction of the colonic strip by acting on the gut's nervous system and acting directly on the smooth muscle in rats with depression.

Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon.

The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium current (I(Ca-L)) prior to and following the application of various concentrations of DCA. The application of DCA (10(-6)-10(-4) M) decreased the amplitude of spontaneous contractions of the PCSM strips in a dose-dependent manner. The administration of DCA (10(-5) M) caused the relaxation of isolated smooth muscle strips pre-contracted by acetylcholine (Ach) or KCl (by 12.2±1.5 and 16.3±6.9%, respectively). The concentration-response curve of CaCl2 was shifted to the right. Pre-treatment of the strips with the protein kinase C (PKC) inhibitor chelerythrine (1 µM) significantly attenuated the effects of DCA on the strips pre-contracted by Ach. DCA reduced the peak I(Ca-L) by 6.02±0.87% at 10(-6) M, 15.02±1.73% at 10(-5) M and 47.14±3.79% at 10(-4) M. DCA shifted the current-voltage (I-V) curve of ICa-L upward, but the contour of the I-V curve was unchanged, and the peak current-induced voltage remained at 0 mV. Pre-treatment with chelerythrine (1 µM) blocked the actions of DCA on the I(Ca-L). Taken together, the actions of DCA on I(Ca-L) in rat colonic SMCs contributed to a negative inotropic effect. These actions appear to be mediated through protein kinase C. Furthermore, this study suggests another possible mechanism for the DCA-related modulation of gastrointestinal motility.