Effect of L-glutamic acid on acid secretion and immunohistochemical localization of glutamatergic neurons in the rat stomach

Glutamatergic neurons in the rat stomach were localized immunohistochemically using antibodies against L-glutamate (L-Glu) as well as glutamate synthesizing enzyme, glutaminase (GLNase). Myenteric ganglia and nerve bundles in the circular muscle and the longitudinal muscle were found to contain GLU- and GLNase-positive nerve fibers, while submucosa and mucosa were devoid of glutamatergic innervation. The distribution of glutamatergic neurons and their processes in both myenteric ganglia and circular muscle is heterogeneous within the stomach. The effect of L-Glu on gastric acid secretion was investigated on an everted preparation of isolated rat stomach. L-Glu at 10^-7 and 10^-8 M alone had no effect on acid secretion. It was found that the oxotremorine-, histamine-, or gastrin-stimulated acid secretion was markedly reduced by L-Glu at 10^-8 M, whereas L-Glu had little effect on the acid secretion stimulated by dimethyl-phenylpiperazinium (DMPP) at this concentration. However, at higher concentration, e.g., 10^-7 M, L- Glu also markedly reduced DMPP-induced acid secretion. Among L-Glu receptor agonists tested, quisqualic acid (QA) is most potent, followed by kainic acid (KA) and N-methyl-D-aspartic acid (NMDA) in inhibiting oxotremorine- stimulated acid secretion. Furthermore, this inhibitory effect of L-Glu on oxotremorine-stimulated acid secretion is blocked by 6-cyano-7- nitroquinoxaline-2,3-dione (CNQX), a specific non-NMDA receptor antagonist. All these results suggest that glutamatergic neurons are involved in the modulation of gastric acid secretion via ionotropic QA/KA receptors, probably through openings of Ca²⁺ channels.