Gastric enteric neurones that respond to luminal injury

Challenge of the rat gastric mucosa with HCl stimulates intrinsic neurones in the myenteric plexus of the stomach as demonstrated by immunohistochemical detection of c-Fos. In multiple labelling experiments of whole-mounts and sections of the gastric corpus we determined the chemical code of the stimulated neurones and investigated further whether neural pathways involving capsaicin-sensitive afferents, cholinergic neurones or the vagal system contribute to the stimulation of these neurones. Intragastric (IG) administration of 0.5 m HCl caused c-Fos expression in 12% of myenteric neurones, whereas IG saline failed to induce c-Fos. All stimulated neurones stained for nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), but not for choline acetyltransferase (ChAT). Fibres coexpressing NOS/VIP/NPY were found predominantly in the external muscle layer and the muscularis mucosae of the stomach wall. Pretreatment with capsaicin or hexamethonium, combination of both pretreatments or vagotomy reduced HCl-induced c-Fos expression by 54%, 66%, 63% and 68%, respectively. The data indicate that mucosal acid challenge of the stomach stimulates inhibitory motor neurones in the myenteric plexus and that capsaicin-sensitive afferents as well as cholinergic neurones participate in the neuronal stimulation probably via a vago-vagal reflex.