Effect of Excitatory Amino Acid Neurotransmitters on Acid Secretion in the Rat Stomach

Abstract

Excitatory amino acids (EAAs), in particular, L-aspartate (L-Asp) neurons and their processes, were localized in the rat stomach using a immunohistochemical method with specific antibodies against either L-Asp or its synthesizing enzyme, aspartate aminotransferase (AAT). Myenteric ganglia and nerve bundles in the circular muscle and in the longitudinal muscle were found to be AAT- or L-Asp-positive. In addition, AAT- or L-Asp-positive cells were also found in the muscle layer and the deep mucosal layer. The distribution of AAT- or L-Asp-positive cells in both the mucosal and muscle layers was heterogeneous in the stomach. In addition, L-Asp at 10^–6 M negligibly influenced acid secretion in an everted preparation of isolated rat stomach. However, according to our results, L-Asp markedly inhibited the histamine-stimulated acid secretion, but not the oxotremorine- or the pentagastrin-stimulated acid secretion. Furthermore, L-Asp also inhibited histamine-induced elevation of cAMP. L- Asp itself did not affect the cAMP level although it elevated the cGMP level in the stomach. Moreover, either (+)2-amino-5-phosphonovaleric acid or (±)3-(2-carboxypiperazin-4-yl)prophyl-1-phosphonic acid, i.e. two specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors, blocked the inhibitory effect of L-Asp on histamine-stimulated acid secretion or histamine-induced elevation of cAMP. Since cAMP has been strongly implicated as the second messenger involved in histamine-induced acid secretion, we believe that L-Asp regulates acid secretion in the stomach by inhibiting histamine release through the NMDA receptors, subsequently lowering the level of cAMP and ultimately reducing acid secretion.

Review Article: Glutamate Receptors in Peripheral Tissues: Current Knowledge, Future Research, and Implications for Toxicology

“…Experimental evidence from several labs and from this laboratory ( Figure 7) have shown the GluRs to be present in the stomach, duodenum and descending colon (8,56,74,75,83). Immunohistochemical analysis showed that GluRs antibodies had poor af nity for the esophagus with the exception of anti-NMDAR 1, which preferentially stained the less mature cells within the basal layer of the strati ed squamous epithelium ( Figure 7).…”

“…The studies of Tsai et al (82,83) showed that Glu and Asp are both involved in regulating acid secretion in the stomach. However, their mode of action is different.…”

Non-neuronal glutamate signalling pathways

“…In the stomach, glutamate modulates the ability of histamine to induce acid secretion in the rat and this effect is blocked either by antagonists of AMPA or NMDA receptors [67,68]. In other studies of isolated gut segments from rats, glutamate, NMDA and KA induced concentrationdependent tonic contractions of the gastric fundus, jejunum, ileum and large intestine.…”

A Review of Glutamate Receptors II: Pathophysiology and Pathology

“…In the CNS, electrophysiological L-Glu and L-Asp are less potent than NMDA due to their avid uptake by the tissue 102 , but there appears to be an absence of the uptake processes of these compounds in the myenteric plexus 95,96 . However, Glu and Asp are both involved in regulating acid secretion in the stomach, but the mode of action of each is different 652,658 . Asp was more specific than Glu in regulating acid secretion.…”