EFFECTS OF ORGANOTYPIC CULTURE ON PARASYMPATHETIC INNERVATION OF GUINEA-PIG TRACHEALIS

Nonadrenergic, noncholinergic (NANC) relaxations of airway smooth musc le are thought to be mediated by vasoactive intestinal peptide (VIP) a nd nitric oxide (NO) Previous studies of the parasympathetic innervati on of guinea pig trachealis suggest that the ganglion neurons mediatin g NANC relaxations but not cholinergic contractions are associated wit h the esophagus. In this study, the location of the neurons mediating these responses and their neurochemical phenotype was further assessed . Guinea pig tracheas maintained in organotypic culture for 2 days wit h the adjacent esophagus intact displayed cholinergic contractions and NANC relaxations to electrical field stimulation (EFS) as well as VIP and NO synthase (NOS) nerve fiber densities that were similar to thos e of control tracheas. By contrast, in tracheas cultured without the e sophagus, NANC relaxations to EFS were not observed, and VIP and NOS n erve fiber densities were reduced >80%. EFS-induced cholinergic contra ctions were unaffected by esophagus removal. These results provide fur ther evidence that NANC relaxations are mediated by VIP and NO corelea sed from noncholinergic parasympathetic nerve endings derived from neu rons intrinsic to the esophagus.