TY - JOUR
T1 - SR140333, a substance P receptor antagonist, influences morphological and motor changes in rat experimental colitis
AU - Di Sebastiano, P.
AU - Grossi, L.
AU - Di Mola, F. F.
AU - Angelucci, D.
AU - Friess, H.
AU - Marzio, L.
AU - Innocenti, P.
AU - Büchler, M. W.
PY - 1999
Y1 - 1999
N2 - The etiology of inflammation, edema, and smooth muscle contraction characteristic of inflammatory bowel disease is not clearly understood. There is evidence that several neuropeptides, including substance P (SP), may play a role. In this study we evaluated the ability of a SP-antagonist (SR140333) to modify the course of experimental colitis induced in the rat by trinitrobenzene sulfonic acid (TNB). Colitis was induced in 24 rats using TNB applied by intrarectal enema. Twelve TNB-treated rats received SR140333, 0.1 mg/kg intraperitoneally, 30 min before the administration of TNB and every 48 hr until death. Twelve rats receiving only intrarectal 0.9% saline served as controls. Rats of each group were killed after 14 days. At day 14, the control group showed no signs of inflammation whereas the TNB-treated rats without SR140333 treatment exhibited a well-established colitis. The TNB- treated group had a higher level of inflammation, as seen histologically and by the significantly greater weight of colon strips, compared to the controls (0.30 ± 0.09 g vs 0.13 ± 0.03 g, P < 0.001) and to the SR140333-treated rats (0.30 ± 0.09 g vs 0.14 ± 0.05 g, P < 0.001). In addition, smooth muscle contractility was significantly reduced in the inflamed colons of TNB- treated rats when compared with the controls (carbachol: 42.7 ± 20.3 vs 254.2 ± 69.78 mg/mm2; SP: 18.5 ± 10.02 vs 89.45 ± 23.17 mg/mm2; KCl: 11.4 ± 2.2 vs 98.32 ± 33.57 mg/mm2, P < 0.01). However, SR140333-treated rats showed a recovery from inflammation and motor alterations caused by TNB (carbachol: 150.9 ± 46.1 mg/mm2, P < 0.01; SP: 32.5 ± 9.4 mg/mm2, P < 0.05; KCl: 125.7 ± 36.1 mg/mm2, P < 0.01). In conclusion, treatment with SP antagonist SR140333 reduces the severity of colitis and has beneficial effects on the concomitant alterations of contractility. Thus, the blockade of substance P may represent a possibility in the treatment of intestinal inflammation.
AB - The etiology of inflammation, edema, and smooth muscle contraction characteristic of inflammatory bowel disease is not clearly understood. There is evidence that several neuropeptides, including substance P (SP), may play a role. In this study we evaluated the ability of a SP-antagonist (SR140333) to modify the course of experimental colitis induced in the rat by trinitrobenzene sulfonic acid (TNB). Colitis was induced in 24 rats using TNB applied by intrarectal enema. Twelve TNB-treated rats received SR140333, 0.1 mg/kg intraperitoneally, 30 min before the administration of TNB and every 48 hr until death. Twelve rats receiving only intrarectal 0.9% saline served as controls. Rats of each group were killed after 14 days. At day 14, the control group showed no signs of inflammation whereas the TNB-treated rats without SR140333 treatment exhibited a well-established colitis. The TNB- treated group had a higher level of inflammation, as seen histologically and by the significantly greater weight of colon strips, compared to the controls (0.30 ± 0.09 g vs 0.13 ± 0.03 g, P < 0.001) and to the SR140333-treated rats (0.30 ± 0.09 g vs 0.14 ± 0.05 g, P < 0.001). In addition, smooth muscle contractility was significantly reduced in the inflamed colons of TNB- treated rats when compared with the controls (carbachol: 42.7 ± 20.3 vs 254.2 ± 69.78 mg/mm2; SP: 18.5 ± 10.02 vs 89.45 ± 23.17 mg/mm2; KCl: 11.4 ± 2.2 vs 98.32 ± 33.57 mg/mm2, P < 0.01). However, SR140333-treated rats showed a recovery from inflammation and motor alterations caused by TNB (carbachol: 150.9 ± 46.1 mg/mm2, P < 0.01; SP: 32.5 ± 9.4 mg/mm2, P < 0.05; KCl: 125.7 ± 36.1 mg/mm2, P < 0.01). In conclusion, treatment with SP antagonist SR140333 reduces the severity of colitis and has beneficial effects on the concomitant alterations of contractility. Thus, the blockade of substance P may represent a possibility in the treatment of intestinal inflammation.
KW - Experimental colitis
KW - Histology
KW - Smooth muscle contractility
KW - Substance P receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=0032933192&partnerID=8YFLogxK
U2 - 10.1023/A:1026639509036
DO - 10.1023/A:1026639509036
M3 - Article
C2 - 10063935
AN - SCOPUS:0032933192
SN - 0163-2116
VL - 44
SP - 439
EP - 444
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 2
ER -