COMPARATIVE EFFECTS OF NONPEPTIDE TACHYKININ RECEPTOR ANTAGONISTS ON EXPERIMENTAL GUT INFLAMMATION IN RATS AND GUINEA-PIGS

Previous studies have shown tachykinins implicated in gut inflammation . The aim of this work was to evaluate the effect of treatments with t achykinin NK1, NK2, and NK3 selective receptor antagonists on the deve lopment of gut inflammation induced by trinitrobenzenesulfonic acid (T NBS) in rats and guinea-pigs. On day 0, rats and guinea-pigs received an intraluminal instillation of TNBS/ethanol (40 mg/kg). Each group wa s daily treated with intraperitoneally injected NK1 (SR 140333; 0.3 mg /kg/day), NK2 (SR 48968; 5 mg/kg/day), or NK3 (SR 142801; 1, 5, or 10 mg/kg/day) receptor antagonists or their vehicle. On day 4, inflammato ry levels were evaluated by measuring gut permeability, myeloperoxidas e activity, macro- and microscopic damage scores. In TNBS treated rats , daily administration of SR 140333 (0.3 mg/kg/day) and SR 48968 (5 mg /kg/day) reduced colonic inflammation. In TNBS treated guinea-pigs, da ily administration of SR 48968 (5 mg/kg/day) and SR 142801 (at 5 and 1 0 mg/kg/day) attenuated significantly ileal injury. These results sugg est that non-peptide tachykinin receptor antagonists are potent anti-i nflammatory agents on gut inflammation in rats and guinea-pigs. Howeve r, their activity depends upon the animal species and type of receptor considered.