Role of N‐methyl‐D‐aspartate receptors in gastric mucosal blood flow induced by histamine

Abstract

Ionotropic N-methyl-D-aspartate (NMDA) receptor agonists, L-aspartic acid (L-Asp) and NMDA, have been shown to inhibit histamine-stimulated acid secretion, but their effect on gastric mucosal blood flow (GMBF) is largely unknown. The aim of this study was to investigate whether L-Asp and NMDA inhibit histamine-stimulated GMBF and to examine the expression patterns of NMDA receptor subunits NR1, NR2A, and NR2B in rat stomach. Laser Doppler flowmetry was used to measure gastric blood flow in anesthetized rats. The GMBF was assessed during an intravenous infusion of histamine in the presence of tripelennamine. The effects of L-Asp and NMDA on histamine-induced gastric blood flow were examined. In addition, the distribution patterns of NR1-, NR2A-, and NR2B-contaning NMDA receptors in rat stomach were determined immunohistochemically by using specific antibodies against NR1, NR2A, and NR2B. Histamine-induced enhancement of GMBF depended on acid secretion and the activation of H(2)-receptors. Neither L-Asp nor NMDA had an effect on the spontaneous GMBF. However, L-Asp and NMDA reduced the histamine-induced increase in GMBF. DL-2-amino-5-phosphonopentanoic acid (AP-5), an NMDA receptor antagonist; and prazosin, an alpha(1)-receptor antagonist; but not propanolol, a beta(2)-receptor antagonist; or yohimbine, a alpha(2)-receptor antagonist; reversed the inhibitory effect of L-Asp and NMDA on the histamine-induced increase in GMBF. Therefore, L-Asp and NMDA inhibit histamine-induced GMBF via a mechanism involving the activation of NMDA receptors and alpha(1)- adrenoceptors. The fact that NMDA receptor subunits NR1, NR2A, and NR2B were found to be localized in the rat stomach as visualized immunohistochemically with specific antibodies against NR1, NR2A, and NR2B is consistent with this hypothesis.

Role of taurine on acid secretion in the rat stomach

“…Spontaneous acid secretion from the preparation was 1.232 ± 0.067 μmole/15 min, a value similar to the basal acid secretion in vivo [34] and in vitro [22]. In such preparations, taurine induced acid secretion in a concentration-dependent manner.…”

Function of GABAergic and glutamatergic neurons in the stomach

“…Results from in situ hybridization studies have demonstrated the presence of mRNA for NRl and NMDA [10,11,33] in both myenteric and submucosal ganglia. The distribution pattern of NR1, NR2A and NR2B-containing NMDA receptors in rat stomach is determined immunohistochemically using specific antibodies against NR1, NR2A and NR2B (Figure 3) [34]. These findings are also consistent with the idea that the enteric glutamate receptors are involved in neurogenic motility [15,35] or secretion of the stomach [7,34].…”

“…The distribution pattern of NR1, NR2A and NR2B-containing NMDA receptors in rat stomach is determined immunohistochemically using specific antibodies against NR1, NR2A and NR2B (Figure 3) [34]. These findings are also consistent with the idea that the enteric glutamate receptors are involved in neurogenic motility [15,35] or secretion of the stomach [7,34]. Recently, the NRl subunits have been localized immunohistochemically in peripheral terminals of primary afferent nerves of dorsal root ganglia [34,36].…”

“…These findings suggest that glutamate receptors are involved in the modulation of gastric acid secretion via ionotropic QA/KA receptors, and aspartate regulates acid secretion in the stomach by inhibiting histamine release through the NMDA receptors [7,34,74]. There is also evidence showing a role for enteric ionotropic and metabotropic glutamate receptors in the regulation of acid secretion [7,34,74]. Our recent studies demonstrated that L L -Asp and NMDA, two glutamate receptors agonists, inhibit histamine-induced gastric mucosal blood flow (GMBF) via a mechanism involving the NR1 subunit of NMDA receptors and a 1 -adrenoceptors activation.…”

“…Recently, the NRl subunits have been localized immunohistochemically in peripheral terminals of primary afferent nerves of dorsal root ganglia [34,36]. In addition, the peripheral NMDA receptors are also found in both vagal and spinal primary afferent in the stomach, where the function of NMDA receptors is believed to be involved in gastric motility and gastric secretion [34].…”