DECREASED VASOACTIVE-INTESTINAL-PEPTIDE LEVELS AND GLUTATHIONE DEPLETION IN ACQUIRED MEGACOLON

We reported decreased vasoactive intestinal peptide levels in acquired megacolon. The origin of altered neuropeptide levels is unknown, but recent work suggested that tissue antioxidants may function as neuropr otectants. Our hypothesis was that altered levels of inhibitory neurot ransmitters in human colon are associated with depletion of the tripep tide thiol, glutathione. Normal colon samples (N = 10; from patients 4 1-80 years old) and acquired megacolon samples (N = 10; from patients 31-98 years old) were obtained at surgery. Vasoactive intestinal pepti de levels were decreased in muscularis externa from acquired megacolon (P = 0.01), while there was a modest increase in NADPH diaphorase act ivity in muscularis externa from megacolon (P = 0.10). Glutathione in acquired megacolon was detectable in muscularis externa from only five specimens (P < 0.05), but was not significantly different (P > 0.05) in the mucosal-submucosal layer. The results supported the presence of vasoactive intestinal peptide and NADPH diaphorase in distinct subpop ulations of nerves in human colon. The results also supported the hypo thesis that glutathione functions as a neuroprotectant in a subset of patients with acquired megacolon.