Expression of serotonin receptors in human lower esophageal sphincter

Serotonin (5-HT) is a neurotransmitter and vasoactive amine that is involved in the regulation of a large number of physiological functions. The wide variety of 5-HT-mediated functions is due to the existence of different classes of serotonergic receptors in the mammalian gastrointestinal tract and nervous system. The aim of this study was to explore the expression of multiple types of 5-HT receptor (5-HT_1AR, 5-HT_2AR, 5-HT_3AR, 5-HT₄R, 5-HT_5AR, 5-HT₆R and 5-HT₇R) in sling and clasp fibers from the human lower esophageal sphincter (LES). Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing esophagogastrectomy, and circular muscle strips from the esophagus and stomach were used as controls. Reverse transcription-polymerase chain reaction (RT-PCR), quantitative PCR and western blotting were used to investigate the expression of the various 5-HT receptor types. Messenger RNA for all seven 5-HT receptor types was identified in the sling and clasp fibers of the LES. At the mRNA level, the expression levels were highest for 5-HT_3AR and 5-HT₄R, and lowest for 5-HT_5AR, 5-HT₆R and 5-HT₇R. At the protein level, the expression levels were highest for 5-HT_3AR and 5-HT₄R, followed by 5-HT_1AR and 5-HT_2AR; 5-HT₇R was also detected at a low level. The expression of 5-HT_5AR and 5-HT₆R proteins was not confirmed. The results indicate that a variety of 5-HT receptor types can be detected in the human LES and probably contribute to LES function.