Is glutamate involved in transient lower esophageal sphincter relaxations?
Glutamate is an important excitatory amino acid and plays a major role in brain stem neurotransmission. Although the effect of glutamate on esophageal motility is well studied, its role in the triggering of transient lower esophageal sphincter relaxations (TLESRs) remains to be determined. Esophageal manometry was performed in 10 healthy volunteers using a perfused sleeve assembly. The effect of intragastric instillation of the nonspecific N-methyl-D-aspartate receptor antagonist dextromethorphan (30 mg) and the glutamate-release inhibitor riluzole (100 mg) was evaluated on esophageal motility and on the rate of TLESRs during isovolumetric gastric distension (500 ml). Dextromethorphan and riluzole had no effect on the amplitude or peristaltic velocity of esophageal pressure waves, basal LES pressure, or LES relaxation after water swallowing. Gastric distension increased the rate of TLESRs from 2.0 (1.0-3.5)/45 min to 5.0 (4.0-7.0)/45 min during placebo (P < 0.05). In contrast, the rate of TLESRs during gastric distension was significantly reduced with riluzole [4.0 (2.5-6.0)/45 min], but not with dextromethorphan. In conclusion, riluzole had no effect on swallow-induced LES relaxation, esophageal peristalsis, or gastric tone, but it reduced the number of TLESRs evoked by gastric distension. These findings suggest that glutamate may be involved in the neurocircuitry underlying TLESRs. However, as the effect was only marginal, additional studies are required to confirm our observations.
Hirsch
D P
DP
Division of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Tytgat
G N J
GN
Boeckxstaens
G E E
GE
D000328:Adult; D003679:Deglutition; D003915:Dextromethorphan / Q000494:pharmacology; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D008297:Male; D008365:Manometry; D009126:Muscle Relaxation / Q000187:drug effects; D010528:Peristalsis / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D019782:Riluzole / Q000494:pharmacology; D012677:Sensation; D013270:Stomach / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003915:Dextromethorphan; D019782:Riluzole