The potential role of thyrotropin-releasing hormone in colonic dysmotility induced by water avoidance stress in rats

TRH may be involved in the dysmotility induced by chronic stress and may have some potential clinical therapeutic use in regulating gut motility.

Male SD rats were exposed to daily 1-h WAS or sham WAS for 10 consecutive days. The presence of TRH in the serum and colonic mucosa were determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to detect the expression of TRH receptor 1 (TRH-R1). The contractions of proximal colonic smooth muscle were studied in an organ bath system. The whole-cell patch-clamp technique was used to record the currents of both L-type calcium currents (ICa,L) and large conductance Ca2+-activated K+ (BKCa) channels in colonic smooth muscle cells (SMCs) isolated from adult rats.

This study sought to investigate the effect and underlying mechanism of thyrotrophin releasing hormone (TRH) on colonic contractile disorders induced by chronic water avoidance stress (WAS).

Enzyme immunoassay revealed that TRH was present in both serum and colonic mucosa and that this expression increased in the WAS group. Immunohistochemistry revealed that the TRH-R1 level increased in colons devoid of mucosa and submucosa from the stressed rats as compared with the control group. TRH increased the spontaneous contractions of the longitudinal muscle and circular muscle strips in a dose-dependent manner in vitro. The effect was also confirmed in an vivo experiment, where an intraperitoneal injection of TRH in rats significantly increased fecal pellet output during a 24-h period as compared with the control group. Furthermore, intraperitoneal injection of a non-specific TRH receptor antagonist, chlordiazepoxide and a TRH-R1 antibody, partially decreased the fecal pellets of WAS rats during the 10-day stress period. Furthermore, TRH increased the peak current of L-type channels in colonic smooth muscle cells (SMCs) at a membrane potential of 0 mV, while the current of large conductance Ca2+-activated K+ (BKCa) channels was not changed following the addition of TRH.