SUBSTANCE P RECEPTOR ANTAGONIST
SMOOTH MUSCLE CONTRACTILITY
Springer Online Journal Archives 1860-2000
Abstract The etiology of inflammation, edema, and smoothmuscle contraction characteristic of inflammatory boweldisease is not clearly understood. There is evidencethat several neuropeptides, including substance P (SP), may play a role. In this study weevaluated the ability of a SP-antagonist (SR140333) tomodify the course of experimental colitis induced in therat by trinitrobenzene sulfonic acid (TNB). Colitis was induced in 24 rats using TNB applied byintrarectal enema. Twelve TNB-treated rats receivedSR140333, 0.1 mg/kg intraperitoneally, 30 min before theadministration of TNB and every 48 hr until death. Twelve rats receiving only intrarectal 0.9%saline served as controls. Rats of each group werekilled after 14 days. At day 14, the control groupshowed no signs of inflammation whereas the TNB-treated rats without SR140333 treatment exhibited awell-established colitis. The TNB-treated group had ahigher level of inflammation, as seen histologically andby the significantly greater weight of colon strips, compared to the controls (0.30 ± 0.09 gvs 0.13 ± 0.03 g, P 〈 0.001) and to theSR140333-treated rats (0.30 ± 0.09 g vs 0.14± 0.05 g, P 〈 0.001). In addition, smoothmuscle contractility was significantly reduced in the inflamedcolons of TNB-treated rats when compared with thecontrols (carbachol: 42.7 ± 20.3 vs 254.2± 69.78 mg/mm2± 10.02 vs 89.45± 23.17 mg/mm2 11.4 ± 2.2 vs 98.32 ± 33.57mg/mm21). However, SR140333-treated ratsshowed a recovery from inflammation and motoralterations caused by TNB (carbachol: 150.9 ±46.1 mg/mm21; SP: 32.5 ± 9.4 mg/mm25; KCl:125.7 ± 36.1 mg/mm21). In conclusion,treatment with SP antagonist SR140333 reduces theseverity of colitis and has beneficial effects on theconcomitant alterations of contractility. Thus, theblockade of substance P may represent a possibility inthe treatment of intestinal inflammation.
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