Piebald mice inherit congenital megacolon associated with distal aganglionosis. To study the distribution of intrinsic peptidergic nerves in the gut of piebald mice and their normal littermates, we used specific radioimmunoassays to measure the tissue concentrations of the following immunoreactive neuropeptides: vasoactive intestinal peptide (VIP), peptide histidine-isoleucine (PHI), [Met]enkephalin (Enk), substance P (SP), and bombesin-like intestinal peptide (BLIP). In the normal littermates, all neuropeptide concentrations were significantly greater in the colon than in the proximal gut. SP, Enk, VIP, PHI, and BLIP levels were all decreased in the distal colon of piebald mice as compared to normal littermates. SP, BLIP, and Enk levels were also decreased in the dilated proximal colon of piebald mice. These results suggest that there are abnormalities in the peptidergic innervation of the proximal and the distal colon in piebald mice. The abnormalities localized to the proximal colon of piebald mice may be related to functional obstruction of the colon.
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