Role of kinin B-1 and B-2 receptors and mast cells in post intestinal infection-induced hypersensitivity to distension

Distension of the rat intestine causes a capsaicin-sensitive, pressure-depe ndent depressor response which is indicative of nociception. A hypersensiti vity of jejunal distension which possibly involves tachykinin NK2 receptors and is restricted to areas with mast cell hyperplagia is observed in rats infected 30 days previously with Nippostrongylus brasiliensis. This study a imed to further investigate the role of mast cells, tachykinins and kinins in this intestinal hypersensitivity. The activity of a mast cell stabilizer (doxantrazole), kinin antagonists (des-Arg 10-[Leu9]-kallidin, B-1, HOE 14 0, B-2) and tachykinin antagonists (CP 99, 994, NK1, SR 142801, NK3) were t ested against the distension-induced depressor responses in control and pos t-infected rats. The 30-day post-infection-induced hypersensitivity was sig nificantly reduced by the mast cell stabilizer doxantrazole. The hypersensi tivity had resolved in 90-day post-infected rats when mast cells levels had normalized. Des-Arg 10-[Leu9]-kallidin and HOE 140 did not inhibit the dep ressor responses in controls but produced a significant inhibition in 30-da y post-infected rats. CP 99,994 inhibited the depressor responses in post-i nfected rats with an equal potency to that in control rats. SR 142801 was i nactive in both groups. In conclusion, mast cells and kinin-mediated nocice ption appear to be involved in post-infection intestinal hypersensitivity w hereas tachykinin NK1 and NK3 receptors do not.