d-serine modulates non-adrenergic non-cholinergic contraction of lower esophageal sphincter in rats

• Published in: European journal of pharmacology 2012-12, Vol.696 (1-3), p.155-160
• Main Authors: Ghasemi-Kasman, Maryam, Dehpour, Ahmad R., Mani, Ali R.
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Animals; antagonists; central nervous system; D-Amino-Acid Oxidase - genetics; D-Amino-Acid Oxidase - metabolism; d-Serine; electric field; enzymes; esophageal sphincter; Esophageal Sphincter, Lower - drug effects; Esophageal Sphincter, Lower - physiology; In Vitro Techniques; Liver - metabolism; Lower esophageal sphincter; Male; metabolism; Muscle Contraction - drug effects; NMDA receptor; pharmacology; Racemases and Epimerases - genetics; Racemases and Epimerases - metabolism; Rat; Rats; Rats, Wistar; receptors; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; reverse transcriptase polymerase chain reaction; serine; Serine - pharmacology; Serine racemase; Western blotting
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.09.011

Endogenous d-serine is known to modulate glutamatergic transmission via interaction with the glycine site of N-methyl-d-aspartate (NMDA) receptors. d-serine is synthesized by racemization of l-serine using an enzymatic reaction catalyzed by serine racemase. Although much attention has been focused on the role of d-serine within the central nervous system, the physiological role of d-serine in enteric nervous system has not been investigated. Lower esophageal sphincter (LES) function is known to be modulated by NMDA-dependent mechanisms. The present study was aimed to study the expression of enzymes involved in d-serine metabolism and the function of d-serine in lower esophageal sphincter in rats. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting showed the expression of serine racemase in isolated rat LES. Electrical field stimulation was used to induce non-adrenergic non-cholinergic (NANC) contraction/relaxation of isolated rat LES in an organ bath using an isometric force transducer. The organ bath studies on isolated rat LES showed that incubation with d-serine (100μM) is associated with a significant increase in the NANC contraction of isolated LES. This effect of exogenous d-serine was inhibited by NMDA receptor antagonists (MK-801), suggesting that NMDA receptors are involved in the effects of d-serine on NANC contraction of LES. Incubation with d-serine did not show a significant effect on NANC relaxation within our experimental setting. The results of this study suggest that serine racemase is expressed in LES and d-serine modulates contraction of the lower esophageal sphincter in rats.