Functional response to vasoactive intestinal peptide in piebald lethal mice.

Diminished concentrations of the gut neuropeptide, vasoactive intestinal peptide (VIP), have been measured by radioimmunoassay in man and mouse models of Hirschsprung's disease. This in vitro study was designed to ascertain the functional response to VIP in aganglionic colon. Seven piebald lethal (PLM) mice with histologically verified aganglionosis and seven normal littermates (NLM) were sacrificed. Distal colonic segments were placed in standard oxygenated tissue baths and responses to electrical field stimulation (EFS), acetylcholine (ACh), and VIP recorded and analyzed by a motility index (MI). Aganglionic colonic tissues from PLM exhibited marked basal contractile activity in contrast to NLM (MI = 19.5 +/- 2.0 SEM v 6.5 +/- 3.6 SEM, P less than .01). In NLM tissues, VIP reduced the MI to ACh challenge by 49% (P less than .01), while in PLM tissues, a nonsignificant 22% reduction was observed. VIP blocked the response to EFS in NLM tissues, while no response was elicited to EFS in PLM tissues. An in vitro deficit in the VIP inhibitory response to ACh challenge is apparent in PLM with distal colonic aganglionosis. The increased basal activity and reduction in responsiveness to VIP, observed in the PLM tissues, support a generalized reduction in the function of the inhibitory innervation of the aganglionic colon.