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. 2024 May 1:15:1389873.
doi: 10.3389/fphar.2024.1389873. eCollection 2024.

Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats' nucleus ambiguus

Hongzhao Sun  1 , Chenyu Li  1 , Yuan Shi  1 , Yiya Wang  1 , Jinjin Li  1 , Linkun Fan  1 , Yan Yu  1 , Xiaofeng Ji  1 , Xiaoting Gao  1 , Keyuan Hou  1 , Yuxue Li  1
Affiliations

Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats' nucleus ambiguus

Hongzhao Sun et al. Front Pharmacol. .

Abstract

Background: In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function.

Methods: Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value.

Results: Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05).

Conclusion: The results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function.

Keywords: L-glutamate; gastric acid secretion; gastric motility; hydrogen sulfide; nucleus ambiguus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Histological identification of microinjection, the location of the nucleus ambiguus (NA) in the brain. ×40 (A) A brain section stained with neutral red. The blue dot represents injection into the NA. (B) The position of the NA in the brain atlas.
FIGURE 2
FIGURE 2
Effect of L-glutamate (L-Glu) microinjection in nucleus ambiguus (NA) on gastric motility in rats. (A) The gastric motility curve of physiological saline (PS) group, (B) The gastric motility curve of L-Glu group, (C) The gastric motility curve of D-2-amino-5-phopho-novalerate (D-AP5) + L-Glu group, and (D) The gastric motility curve of aminooxyacetic acid (AOAA) + L-Glu group (E) Average duration of contraction waves (A.D.C.W). data before and after microinjection of PS, L-Glu, D-AP5 + L-Glu and AOAA + L-Glu (n = 6). (F) Average amplitude of contraction waves (A.A.C.W) data before and after microinjection of PS, L-Glu, D-AP5 + L-Glu and AOAA + L-Glu (n = 6). (G) Average gastric motility index (A.G.M.I) data before and after microinjection of PS, L-Glu, D-AP5 + L-Glu and AOAA + L-Glu (n = 6). **p < 0.01,*p < 0.05, after microinjection compared with before microinjection.
FIGURE 3
FIGURE 3
Effect of NaHS microinjection in nucleus ambiguus (NA) on gastric motility in rats. (A) The gastric motility curve of physiological saline (PS) group, (B) The gastric motility curve of NaHS group, and (C) The gastric motility curve of D-2-amino-5-phopho-novalerate (D-AP5) + NaHS (D) Average duration of contraction waves (A.D.C.W). data before and after microinjection of PS, NaHS and D-AP5 + NaHS (n = 6). (E) Average amplitude of contraction waves (A.A.C.W) data before and after microinjection of PS, NaHS and D-AP5 + NaHS (n = 6). (F) Average gastric motility index (A.G.M.I) data before and after microinjection of PS, NaHS and D-AP5 + NaHS (n = 6). **p < 0.01,*p < 0.05, after microinjection compared with before microinjection.
FIGURE 4
FIGURE 4
The gastric motility inhibition rate of L-glutamate (L-Glu), D-2-amino-5-phopho-novalerate (D-AP5) + L-Glu, aminooxyacetic acid (AOAA) + L-Glu, NaHS, D-AP5 + NaHS and physiological saline (PS) groups (n = 6) (A) Average duration of contraction waves (A.D.C.W). inhibition rate in each group. (B) Average amplitude of contraction waves (A.A.C.W) inhibition rate in each group. (C) Average gastric motility index (A.G.M.I) inhibition rate in each group. Different letters between two groups indicate a significant difference (p < 0.05).
FIGURE 5
FIGURE 5
Effects of nucleus ambiguus (NA) injection of physiological saline (PS), L-glutamate (L-Glu), D-2-amino-5-phopho-novalerate (D-AP5) + L-Glu and aminooxyacetic acid (AOAA) + L-Glu on gastric acid secretion (n = 6). **p < 0.01, after microinjection compared with before microinjection.
FIGURE 6
FIGURE 6
Effects of nucleus ambiguus (NA) injection of physiological saline (PS), NaHS and D-2-amino-5-phopho-novalerate (D-AP5) + NaHS on gastric acid secretion (n = 6). **p < 0.01, after microinjection compared with before microinjection.
FIGURE 7
FIGURE 7
The gastric acid secretion promotion rate of L-glutamate (L-Glu), D-2-amino-5-phopho-novalerate (D-AP5) + L-Glu, aminooxyacetic acid (AOAA) + L-Glu, NaHS, D-AP5 + NaHS and physiological saline (PS) groups (n = 6). Different letters between two groups indicate a significant difference (p < 0.05).
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