title: D-serine modulates non-adrenergic non-cholinergic contraction of lower esophageal sphincter in rats.
abstract: 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 (100 μM) 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.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghasemi-Kasman
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
authors.forename: Ali R
authors.initials: AR
authors.lastname: Mani
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000378:metabolism; D049630:Esophageal Sphincter, Lower / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012694:Serine / Q000494:pharmacology*; D000099300:Serine Racemase
chemical_list: D000199:Actins; D003605:D-Amino-Acid Oxidase; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase