Abstract
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-HT1AR, 5-HT2AR, 5-HT3AR, 5-HT4R, 5-HT5AR, 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-HT3AR and 5-HT4R, and lowest for 5-HT5AR, 5-HT6R and 5-HT7R. At the protein level, the expression levels were highest for 5-HT3AR and 5-HT4R, followed by 5-HT1AR and 5-HT2AR; 5-HT7R was also detected at a low level. The expression of 5-HT5AR 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.
Highlights
Serotonin (5-hydroxytryptamine, 5-HT) has important biological functions that are mediated via 5-HT receptors
The majority of 5-HT in the body is produced by enterochromaffin cells in the gut. 5-HT receptors are widely distributed in the gastrointestinal mucosa and muscle layers, and play an important role in the functional mediation of the gastrointestinal tract [2]
Abnormalities in the lower esophageal sphincter (LES) are closely associated with dysfunction in gastrointestinal motility disorders such as achalasia and gastroesophageal reflux disease (GERD) [4]
Summary
Serotonin (5-hydroxytryptamine, 5-HT) has important biological functions that are mediated via 5-HT receptors. Seven families of 5-HT receptors, designated from 5-HT1 to 5-HT7, are currently recognized and more than sixteen subtypes have been identified in humans. 5-HT receptors are widely distributed in the gastrointestinal mucosa and muscle layers, and play an important role in the functional mediation of the gastrointestinal tract [2]. It has been found that 5-HT receptors are widely expressed in the gastrointestinal tracts of mammals, such as the rat and opossum [3]. There is little information available concerning 5-HT receptor expression in the human lower esophageal sphincter (LES). The LES is an important physiological structure at the esophagogastric junction. Abnormalities in the LES are closely associated with dysfunction in gastrointestinal motility disorders such as achalasia and gastroesophageal reflux disease (GERD) [4]
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