FUNCTIONAL AND MORPHOLOGICAL EXAMINATION OF GANGLIONIC AND AGANGLIONIC DISTAL GUT FROM THE LETHAL SPOTTED MOUSE

The aim of the study was to evaluate both morphologically and function ally the distal large intestine from the aganglionic lethal spotted (l s/ls) mutant mouse and their healthy litter mates. Immunohistochemical ly, the aganglionic murine distal large intestine showed an absence of nerve cell bodies, and a reduction or absence of nerve fibers display ing immunoreactivity (IR) for protein gene product (PGP), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP) , galanin and calcitonin gene-related peptide (CGRP), while in the gan glionic large intestine these neuronal populations were abundantly pre sent throughout the gut wall. Pathological nerve trunks within the aff licted intestinal segment were found to harbour PGP- and neuropeptide Y (NPY)-IR nerve fibers. Smooth muscle specimens from the distal part of the murine distal large intestine were mounted as ring preparations in vitro and subjected to electrical field stimulation (EFS), EFS (4- 20 Hz) caused a contraction in both ganglionic and aganglionic intesti ne. After pretreatment with atropine EFS (20 Hz) evoked a biphasic mot or response, a relaxation followed by a contraction in control specime ns, while no motor response was seen in aganglionic intestine. Additio n of the NOS-inhibitor N-nitro-L-arginine methyl ester (L-NAME) caused per se a weak and transient contraction and reduced the amplitude of the EFS-induced relaxation in control intestine.