EXPRESSION OF MESSENGER-RNA FOR VASOACTIVE - INTESTINAL PEPTIDE IN NORMAL HUMAN COLON AND DURING INFLAMMATION

The availability of colon provides a ready source of human neurons. Am ong the products of nerve cell bodies, vasoactive intestinal peptide i s a neuropeptide that serves as a marker of non-adrenergic, non-cholin ergic inhibitory nerves in colon. These nerves have been proposed to b e involved in regulation of immune function, secretion, and smooth mus cle function. In previous work, we identified decreased tissue levels of vasoactive intestinal peptide in a disorder of chronic colonic muco sal inflammation, ulcerative colitis. We hypothesized that diminished gene expression of vasoactive intestinal peptide could result in decre ased tissue levels of this neuropeptide. Sigmoid colon was obtained at surgery from controls (n = 6) and patients with ulcerative colitis (n = 6). Vasoactive intestinal peptide mRNA was quantified by Northern b lot hybridization and tissue levels of vasoactive intestinal peptide w ere determined by radioimmunoassay. Tissue vasoactive intestinal pepti de was decreased only in the mucosal-submucosal layer of ulcerative co litis (p = .02). There was a single 1.7 kbase vasoactive intestinal pe ptide transcript identified in both control colon and ulcerative colit is. Normalized vasoactive intestinal peptide mRNA levels were increase d by 260% in ulcerative colitis compared to controls (p < .01). These observations suggest that decreased vasoactive intestinal peptide gene expression or abnormal post-transcriptional processing are not primar y defects in this disorder of chronic inflammation. The findings suppo rt the alternative hypothesis that axonal degeneration in ulcerative c olitis could result in increased expression of neuronal vasoactive int estinal peptide mRNA.