Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease.

Abstract

Several lines of evidence indicate that tachykinin neuropeptides [substance P (SP), substance K (SK), and neuromedin K (NK)] play a role in regulating the inflammatory and immune responses. To test this hypothesis in a human inflammatory disease, quantitative receptor autoradiography was used to examine possible abnormalities in tachykinin binding sites in surgical specimens from patients with inflammatory bowel disease. Surgical specimens of colon were obtained from patients with ulcerative colitis (n = 4) and Crohn disease (n = 4). Normal tissue was obtained from uninvolved areas of extensive resections for carcinoma (n = 6). In all cases, specimens were obtained <5 min after removal to minimize influences associated with degradation artifacts and were processed for quantitative receptor autoradiography by using '2I-labeled Bolton-Hunter conjugates of NK, SK, and SP. In the normal colon a low concentration of SP receptor binding sites is expressed by submucosal arterioles and venules and a moderate concentration is expressed by the external circular muscle, whereas SK receptor binding sites are expressed in low concentrations by the external circular and longitudinal muscle. In contrast, specific NK binding sites were not observed in any area of the human colon. In colon tissue obtained from ulcerative colitis and Crohn disease patients, however, very high concentrations of SP receptor binding sites are expressed by arterioles and venules located in the submucosa, muscularis mucosa, external circular muscle, external longitudinal muscle, and serosa. In addition, very high concentrations of SP receptor binding sites are expressed within the germinal center of lymph nodules, whereas the concentrations of SP and SK binding sites expressed by the external muscle layers are not altered significantly. These results demonstrate that receptor binding sites for SP, but not SK or NK, are ectopically expressed in high concentrations (1000 -2000 times normal) by cells involved in mediating inflammatory and immune responses. These data suggest that SP may be involved in the pathophysiology of inflammatory bowel disease and might provide some insight into the interaction between the nervous system and the regulation of inflammation and the immune response in human inflammatory disease.identified within a subpopulation of these sensory neurons (1). The most extensively characterized of these sensory neuropeptides is substance P (SP), a member of the mammalian tachykinin family (Fig. 1), which also includes SK and NK. Though it is clear that SP and SK are expressed by sensory neurons (2) this remains uncertain for NK and derives from difficulty in generating highly specific antibodies for each of the tachykinins since they all share the highly antigenic carboxyl terminus -Phe-Xaa-Gly-Leu-Met-NH2,

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

“…In inflammatory bowel disease, a 1000-fold increase in the number of NK1 receptors on small bowel blood vessels has been described. 24,25) Therefore substance P may not only play a role in the mediation of peristaltic contractions, but also a pathophysiologic role in the increased blood flow in the small intestine. 8) However, since there are no findings that the increase in intestinal blood flow by DKCT is related to substance P and that it participates in the physiologic regulation of mucosal blood flow in the gastrointestinal tract, further studies are needed.…”

Substance P Regulates Th1-Type Colitis in IL-10 Knockout Mice

“…Human IBD probably results from a dysregulated mucosal immune response to normal intestinal bacteria. In human IBD there is increased NK-1R mRNA expression (9) in the tissue. Goode et al (10) showed, using quantitative PCR, a 7-fold increase in NK-1R transcripts in CD colon and a somewhat more modest increase in ulcerative colitis.…”

Roles of Substance P Receptors in Human Colon Circular Muscle: Alterations in Diverticular Disease

“…These receptors have been localized autoradiographically on the circular muscle and muscularis mucosae (Gates et al, 1989;Warner et al, 2000). The actions of NK-1 receptors in human colon, on the other hand, are more diverse because immunohistochemical and autoradiographic studies have shown that NK-1 receptors are expressed on a variety of cell types, including smooth muscle, neurons, immune cells, glands, and vascular endothelium (Mantyh et al, 1988;Goode et al, 2000a;Renzi et al, 2000), implying that NK-1 receptors may be involved in the control of smooth muscle excitation, immune responses, secretion, and blood flow.…”