Effects of tegaserod on visceral sensitivity and expression of SP and CGRP in the rat colon

Objective: To investigate the effects of tegaserod on visceral sensitivity and explore the regulating mechanism. Methods: Forty-two male Spragre-Dawley rats, which were induced colonic inflammation by intraluminal administration of trinitrobenzenesulfonic acid (TNBS), were randomly divided into eight groups. In the three colorectal distention (CRD) treated groups (n = 6), abdominal contractions were recorded after 3, 7 and 14 days of intra-gastric administration of tegaserod 2 mg/kg d. In the three CRD control groups (n = 4), abdominal contractions were recorded after 3, 7 and 14 days of intra-gastric injection of saline 2.0 mL/d. In immunohistochemistry (IH) treated group (n = 6) and IH control group (n = 6), samples of colon were removed and processed for SP and CGRP immunohistochemistry after 7 days of intra-gastric administration of tegaserod and saline, respectively. Results: Abdominal contractions induced by colonic distention decreased significantly at 1.2 mL and 1.6 mL distention volume after 3 days of tegaserod administration (P < 0.05). After 7 and 14 days of intragastric administration of tegaserod, abdominal contractions decreased significantly at 0.4, 0.8, 1.2 mL and 1.6 mL distention volume compared with those of the control rats (P < 0.01). In the rats treated with tegaserod for 7 days, the scoring of substance P in the colon reduced significantly. However, staining of CGRP in the colon did not significantly decrease. Conclusion: Tegaserod can significantly reduce visceral sensitivity to colonic distention in conscious rats. It may reduce visceral sensitivity by inhibiting SP expression of the primary visceral afferents in the colon.

Duke Scholars

Author Li Lan Molecular Genetics and Microbiology