Satoshi Aikiyo1, Kazuhisa Kishi1, Noriyuki Kaji1,2, Shoma Mikawa3, Makoto Kondo4, Shoichi Shimada4, Masatoshi Hori5. 1. Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo, Japan. 2. Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan. 3. Laboratory of Veterinary Clinical Pathology, Faculty of Veterinary Medicine, Okayama University of Science, Ehime, Japan. 4. Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, Japan. 5. Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo, Japan, ahori@mail.ecc.u-tokyo.ac.jp.
Abstract
INTRODUCTION: The serotonin 3A receptor (5-HT3AR) is involved in vomiting and gastrointestinal motility. However, it is not well understood the expression pattern of 5-HT3AR in the gut immunohistochemically and how much contribution of 5-HT3AR to upper or lower intestinal motility. OBJECTIVES: We investigated the contribution of 5-HT3AR to gastrointestinal motor function by using 5-HT3AR KO mice and sought to identify 5-HT3AR-expressing cells via immunohistochemical staining using 5-HT3AR-GFP reporter mice. METHODS: The expression of 5-HT3AR was measured in each section of the gut through real-time PCR. The motor function of the stomach and colon was assessed via the 13C-octanoic acid breath test and colonic bead expulsion test, respectively, using 5-HT3AR KO mice. 5-HT3AR-expressing cells in the muscle layer of the gut were identified by immunohistochemical staining using 5-HT3AR-GFP reporter mice. RESULTS: 5-HT3AR was expressed throughout the digestive tract, and 5-HT3AR expression in the stomach and lower digestive tract was higher than that in the other sections. Motor function in the stomach and colon was lower in 5-HT3AR KO mice than in WT mice. As a result of immunohistochemical staining using GFP reporter mice, cholinergic neurons and PDGFRα+ cells were shown to express 5-HT3AR. In contrast, 5-HT3AR indicated by GFP fluorescence was rarely detected in ICC and smooth muscle cells. CONCLUSIONS: These results show that 5-HT3AR is highly expressed in the stomach and large intestine and that the activation of 5-HT3AR accelerates gastric emptying and large intestine transit. Additionally, 5-HT3AR is highly expressed in cholinergic neurons and some interstitial cells, such as PDGFRα+ cells.
INTRODUCTION: The serotonin 3A receptor (5-HT3AR) is involved in vomiting and gastrointestinal motility. However, it is not well understood the expression pattern of 5-HT3AR in the gut immunohistochemically and how much contribution of 5-HT3AR to upper or lower intestinal motility. OBJECTIVES: We investigated the contribution of 5-HT3AR to gastrointestinal motor function by using 5-HT3AR KO mice and sought to identify 5-HT3AR-expressing cells via immunohistochemical staining using 5-HT3AR-GFP reporter mice. METHODS: The expression of 5-HT3AR was measured in each section of the gut through real-time PCR. The motor function of the stomach and colon was assessed via the 13C-octanoic acid breath test and colonic bead expulsion test, respectively, using 5-HT3AR KO mice. 5-HT3AR-expressing cells in the muscle layer of the gut were identified by immunohistochemical staining using 5-HT3AR-GFP reporter mice. RESULTS:5-HT3AR was expressed throughout the digestive tract, and 5-HT3AR expression in the stomach and lower digestive tract was higher than that in the other sections. Motor function in the stomach and colon was lower in 5-HT3AR KO mice than in WT mice. As a result of immunohistochemical staining using GFP reporter mice, cholinergic neurons and PDGFRα+ cells were shown to express 5-HT3AR. In contrast, 5-HT3AR indicated by GFP fluorescence was rarely detected in ICC and smooth muscle cells. CONCLUSIONS: These results show that 5-HT3AR is highly expressed in the stomach and large intestine and that the activation of 5-HT3AR accelerates gastric emptying and large intestine transit. Additionally, 5-HT3AR is highly expressed in cholinergic neurons and some interstitial cells, such as PDGFRα+ cells.