Expression of serotonin receptor HTR4 in glucagon-like peptide-1-positive enteroendocrine cells of the murine intestine
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ORGAN PHYSIOLOGY
Expression of serotonin receptor HTR4 in glucagon-like peptide-1-positive enteroendocrine cells of the murine intestine Motoshi Okumura 1 & Akihiro Hamada 1 & Fumina Ohsaka 2 & Takeshi Tsuruta 3 & Tohru Hira 4 & Kei Sonoyama 4,5 Received: 2 July 2020 / Revised: 30 July 2020 / Accepted: 14 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 GLP1 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. Keywords Serotonin, . Glucagon-like peptide-1, . Enteroendocrine cells, . Enterochromaffin cells Motoshi Okumura and Akihiro Hamada contributed equally to this work. A Commentary to this article is available online at https://doi.org/10. 1007/s00424-020-02454-6 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00424-020-02453-7) contains supplementary material, which is available to authorized users. * Kei Sonoyama [email protected] 1
Graduate School of Life Science, Hokkaido University, Sapporo 060-8589, Japan
2
Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan
3
Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan
4
Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan
5
Laboratory of Food Biochemistry, Research Faculty of Agriculture, Ho
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