Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation

Background-Substantial evidence implicates the neuropeptide substance P (SP ) in mucosal immunoinflammatory responses. Autoradiographic studies have su ggested a disturbance in SP receptor expression in inflammatory bowel disea se (IBD). Aims-Because of technical limitations such as poor cellular resolution with autoradiography, we used molecular methods to specifically localise the ce llular expression of the neurokinin-l receptor (NK-1R) in IBD colon, and to quantitate NK-1R mRNA expression levels therein. Methods-In situ hybridisation and immunohistochemistry were used to localis e NK-1R mRNA and protein, respectively, in normal, ulcerative colitis (UC), and Crohn's disease (CD) colonic resections. NK-1R mRNA expression levels of normal, UC, and CD mucosal biopsies were quantitated by competitive reve rse transcription-polymerase chain reaction. Results-NK-1R expression was localised to lamina propria mononuclear cells, epithelium, submucosal vasculature, smooth muscle, and myenteric plexus of normal and IBD colon. No ectopic NK-1R expression was observed in IBD. How ever, we found increased numbers of NK-1R expressing lymphoid cells in IBD tissue, aberrant negative epithelial expression of NK-1R in UC, and increas ed expression of NK-1R in CD myenteric plexus. Quantitation of NK-1R mRNA e xpression in IBD colonic mucosal biopsies revealed marked upregulation of N K-1R mRNA levels compared with non-inflamed mucosal expression levels (p<0. 01). Conclusions-This report demonstrates the strategic localisation and upregul ation of NK-1R expression in IBD colon, and thereby suggests the involvemen t of substance P in the pathophysiological symptoms of IBD.