Ontogeny of neurohormonal peptides, serotonin, and nitric oxide synthase in the gastrointestinal neuroendocrine system of the axolotl (Ambystoma mexicanum): An immunohistochemical analysis

The ontogeny of the neurohormonal peptides vasoactive intestinal polypeptid e (VIP), neurotensin (NT), substance P (SP), calcitonin gene-related peptid e (CGRP), gastrin/cholecystokinin (GAS/CCK), and somatostatin (SOM) as well as serotonin (SER) and nitric oxide synthase (NOS) was investigated in the gastrointestinal tract of the urodele Ambystoma mexicanum, the axolotl, us ing immunohistochemical techniques. The first regulatory substances to appe ar were SP, SOM, and SER that could be immunohistochemically detected up fr om stage 1. At early stage 2, VIP immunoreactivity was observed infrequentl y in enteric nerve fibers. With the onset of external feeding at late stage 2, SP-immunoreactive (IR) and SER-IR endocrine cells and VIP-IR nerve fibe rs were present throughout the gastrointestinal tract. Furthermore, in the small intestine NT-IR and GAS/CCK-IR endocrine cells appeared. At stage 3, SER immunoreactivity was observed not only in endocrine cells but also in n erve fibers. CGRP-IR and SP-IR nerve fibers were detectable at stage 4 and stage 5, respectively. From stage 5 on, a minority of the CGRP immunoreacti vity occurred in SP-IR nerve fibers. NOS immunoreactivity did not appear be fore stage 6 when it was found infrequently in nerve fibers. Thus, several phases of development can be distinguished: (1) at the yolk sac stages only few regulatory substances are present. (2) At the onset of external feedin g, all endocrine cell types investigated were readily detectable. Thus, the onset of external feeding seems to trigger the development of the gastroin testinal endocrine system. (3) The endocrine cells are first found in the p roximal part of the gastrointestinal tract and later in higher numbers in t he distal parts. (4) The dually distributed neurohormonal peptides and SER first appear in endocrine cells and later additionally in nerve fibers. Thu s, the nerve fibers likely set up the fine regulation of gastrointestinal b lood flow and motility. (C) 2001 Academic Press.