ACQUIRED MEGACOLON IS ASSOCIATED WITH ALTERATION OF VASOACTIVE-INTESTINAL-PEPTIDE LEVELS AND ACETYLCHOLINESTERASE ACTIVITY

Based upon previous morphologic studies, we hypothesized that the deve lopment of acquired megacolon was associated with abnormalities of ent eric neurotransmitter concentrations and enzymatic activities. Specime ns were obtained at surgery from patients with normal descending-sigmo id colon (n = 13) and patients with sigmoid megacolon (n = 6; defined by radiologic measurement). Radioimmunoassays were used to measure the non-adrenergic, non-cholinergic inhibitory neuropeptide, vasoactive i ntestinal peptide, and the non-adrenergic, non-cholinergic excitatory neuropeptide, substance P, while spectrophotometric assays were used t o quantitate acetylcholinesterase activity and choline acetyltransfera se activity. There were significantly decreased concentrations of vaso active intestinal peptide and decreased acetylcholinesterase activity in muscularis externa from patients with acquired megacolon. In megaco lon, vasoactive intestinal peptide-containing nerve fibers appeared to be diminished in circular and longitudinal smooth muscle, and immunos taining of nerve cell bodies in the plexus submucosus externus appeare d diminished. These results suggest the hypothesis that production of vasoactive intestinal peptide is altered allowing secondary colonic hy pertrophy to develop from prolonged cholinergic nerve-mediated contrac tions of circular smooth muscle. As a corollary to this hypothesis, co lonic dilatation might result from prolonged contraction of longitudin al smooth muscle.