Mantyh C R, Vigna S R, Maggio J E, Mantyh P W, Bollinger R R, Pappas T N
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Neurosci Lett. 1994 Sep 12;178(2):255-9. doi: 10.1016/0304-3940(94)90772-2.
Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflammatory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606 abolished saturable 125I-Bolton-Hunter substance P binding to the ectopically expressed receptors in frozen sections of surgically resected bowel from five patients with either Crohn's disease or ulcerative colitis. The rank order of affinity was approximately substance P approximately CP-96,345 approximately L-703,606 > RP-67,580. These results suggest that: (i) the ectopically expressed substance P binding sites in inflammatory bowel disease are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have similar receptor affinities and specificities for substance P and the non-peptide antagonists, and (iii) non-peptide antagonists may be therapeutically beneficial in inflammatory bowel disease by inhibiting the pro-inflammatory effects of substance P acting via the NK-1 receptor.
先前的报告描述了P物质结合位点在炎症性肠病的淋巴样聚集物和小血管上的异位表达。在本报告中，三种非肽类NK-1受体拮抗剂CP-96,345、RP-67,580和L-703,606消除了可饱和的125I-博尔顿-亨特P物质与来自5例克罗恩病或溃疡性结肠炎患者手术切除肠段冰冻切片中异位表达受体的结合。亲和力的排序约为P物质≈CP-96,345≈L-703,606＞RP-67,580。这些结果表明：（i）炎症性肠病中异位表达的P物质结合位点是真正的NK-1受体；（ii）小血管和淋巴样聚集物上所有异位表达的受体以及肠环行肌上正常表达的受体对P物质和非肽类拮抗剂具有相似的受体亲和力和特异性；（iii）非肽类拮抗剂通过抑制P物质经由NK-1受体发挥的促炎作用，可能对炎症性肠病具有治疗益处。
