Substance P (neurokinin-1) and neurokinin A (neurokinin-2) receptor gene and protein expression in the healthy and inflamed human

Increasing evidence suggests that tachykinins are involved in the control o f pathophysiological states, such as inflammation. The precise localization of tachykinin receptors Is of paramount importance in the search for their possible physiological and pathological role; in this study, therefore, we attempted to define cellular sites of substance P (NK-1R) and neurokinin A (NK-2R) receptor expression in the healthy and the inflamed human intestin e by in situ hybridization and immunohistochemistry. In the normal ileum an d colon, NK-1R and NK-2R were localized to smooth muscle cells of the muscu laris mucosae and propria and a few Inflammatory cells of the lamina propri a; NK-1R expression was also found in the muscular wall of submucosal blood vessels, enteric neurons and, to a lesser degree, in surface epithelial ce lls. Patients with Crohn's disease and ulcerative colitis showed a dramatic increase in NK-1R density relative to controls, in both the inflamed and t he uninvolved mucosa, Up-regulation of NK-1R was particularly evident on ep ithelial cells lining the mucosal surface and crypts, as well as on endothe lial cells of capillaries and venules. Also, a marked increase in NK-2R exp ression was found in both groups of patients on inflammatory cells of the l amina propria, especially eosinophils, Our findings demonstrate that in the normal human intestine NK-IR and NK-2R are expressed in multiple cell type s, which are endowed with different physiological functions; in addition, t hey demonstrate that both NK-IR and NK-2R are up-regulated in patients with Crohn's disease and ulcerative colitis. Taken together, these observations may have important physiological and pathophysiological implications, and provide the rationale for the use of NK-1R and NK-2R antagonists in the tre atment of inflammatory bowel disease.