Serotonin (5-hydroxytryptamine [5-HT]) synthesized and released in enterochromaffin (EC) cells participates in various functions in the gastrointestinal tract by acting on a diverse range of 5-HT receptors (HTRs) expressed on smooth muscle, enteric neurons, and epithelial cells. We previously observed that genes encoding HTR2A, HTR2B, and HTR4 are expressed in murine intestinal organoids, suggesting the expression of these HTRs in intestinal epithelial cells. The present study investigated the localization of these HTRs in the murine intestine by immunofluorescence staining. HTR2A, HTR2B, and HTR4 localized in individual solitary cells in the epithelium, while HTR2C was observed in the lamina propria. In the epithelium, HTR2A, HTR2B, and HTR4 colocalized with 5-HT, and HTR4 colocalized with glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). Murine intestinal organoids show a colocalization pattern that is similar to in vivo HTR2A and HTR4 with 5-HT, GLP-1, and PYY. Intraperitoneal and intragastric administration of tegaserod, an HTR4 agonist, failed to alter plasma GLP-1 levels in fasted mice. However, intragastric but not intraperitoneal administration of tegaserod reduced dietary lipid-induced increases of plasma GLP-1 levels. This action of tegaserod was inhibited by co-administration of RS39604, an HTR4 antagonist. These results suggest that murine ileal GLP-1/PYY-producing enteroendocrine (EE) cells express HTR4, while 5-HT-producing EC cells express HTR2A, HTR2B, and HTR4. In addition, the observations regarding in vivo GLP-1 secretion suggest that HTR4 signaling in ileal EE cells suppresses dietary lipid-induced GLP-1 secretion. We thus propose that EC and EE cells may interact with each other through paracrine signaling mechanisms.

合成并在肠嗜铬细胞（EC）细胞中释放的5-羟色胺（5-羟色胺[5-HT]）通过作用于平滑肌，肠神经元，和上皮细胞。我们以前观察到，编码HTR2A，HTR2B和HTR4的基因在鼠肠类器官中表达，表明这些HTR在肠上皮细胞中表达。本研究通过免疫荧光染色研究了这些HTR在鼠肠中的定位。HTR2A，HTR2B和HTR4定位在上皮的单个孤立细胞中，而HTR2C在固有层中观察到。在上皮中，HTR2A，HTR2B和HTR4与5-HT共同定位，而HTR4与胰高血糖素样肽1（GLP-1）和YY肽（PYY）共同定位。鼠肠类器官显示出共定位模式，类似于体内HTR2A和HTR4与5-HT，GLP-1和PYY。HTR4激动剂替加色罗的腹膜内和胃内给药未能改变禁食小鼠的血浆GLP-1水平。然而，胃内而非腹膜内施用替加色罗减少了饮食脂质诱导的血浆GLP-1水平的增加。通过共同施用HTR4拮抗剂RS39604来抑制替加色罗的这种作用。这些结果表明，产生鼠回肠的GLP-1 / PYY肠内分泌（EE）细胞表达HTR4，而产生5-HT的EC细胞表达HTR2A，HTR2B和HTR4。此外，有关体内GLP-1分泌的观察结果表明，回肠EE细胞中的HTR4信号传导可抑制饮食脂质诱导的GLP-1分泌。