Colonic mucosal vasoactive intestinal peptide receptors in malformations of the enteric nervous system are reduced compared with morphologically normal innervated colon

Vasoactive intestinal peptide (VIP) is the most important peptidergic transmitter in intestinal relaxation. VIPergic nerves are reduced in aganglionosis (AG). Corresponding findings in intestinal neuronal dysplasia (IND) are sparse. It is unknown whether superficial mucosal VIP receptors are reduced in AG, IND, or hypoganglionosis (HYP) compared to concentrations in morphologically normal innervated colon (MNIC). Cryostat sections from 38 colonic biopsies (23 patients with AG, IND, or HYP, 15 with MNIC) were incubated with radioactive iodinated (125)I-VIP. Receptors were analyzed by autoradiography. Radioactive-marked receptors trigger the precipitation of metallic silver as silver grains within a photographic emulsion. Grains were quantified by image analysis, calculating the percent covered cell surface. Statistical analysis was done by Mann-Whitney and Kruskal-Wallis tests (significance #E5/E5#<0.05). VIP receptors covered 4.31% of the cell surface in MNIC. The values were significantly reduced in AG (2.72%; #E5/E5#=0.012) and IND (2.93%; #E5/E5#=0.008). The two HYP biopsies showed the lowest values (1.83%). Aganglionic colon could be distinguished from healthy proximal segments and IND from habitual constipation. In AG and IND, even the superficial mucosal VIPergic innervation seems to be impaired. The reduction of mucosal VIP receptors in developmental faults of the enteric nervous system may thus be an indicator of a sensomotor disturbance.