SUBSTANCE-P BINDING-SITES ON INTESTINAL LYMPHOID AGGREGATES AND BLOOD-VESSELS IN INFLAMMATORY BOWEL-DISEASE CORRESPOND TO AUTHENTIC NK-1 RECEPTORS

Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflam matory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606, abolished saturable I-125-Bolton-Hunter substance P binding to the ectopically expressed r eceptors in frozen sections of surgically resected bowel from five pat ients with either Crohn's disease or ulcerative colitis. The rank orde r of affinity was approximately substance P approximate to CP-96,345 a pproximate to L-703,606 > RP-67,580. These results suggest that: (i) t he ectopically expressed substance P binding sites in inflammatory bow el disease are authentic NK-1 receptors, (ii) all ectopically expresse d receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have simila r receptor affinities and specificities for substance P and the non-pe ptide antagonists, and (iii) non-peptide antagonists may be therapeuti cally beneficial in inflammatory bowel disease by inhibiting the pro-i nflammatory effects of substance P acting via the NK-1 receptor.