{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:03:27Z","timestamp":1788620607446,"version":"build-2803163510"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["23K27347"],"award-info":[{"award-number":["23K27347"]}]},{"name":"Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["23KJ0596"],"award-info":[{"award-number":["23KJ0596"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24ama121051j0002"],"award-info":[{"award-number":["24ama121051j0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24ama121051j0003"],"award-info":[{"award-number":["24ama121051j0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23be1004101s0802"],"award-info":[{"award-number":["23be1004101s0802"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24be1004101s0803"],"award-info":[{"award-number":["24be1004101s0803"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Drug-induced emesis is one of the major symptoms of gastrointestinal toxicity. Preclinical risk assessment of emesis has been challenging owing to the lack of suitable animal models or in vitro assay systems. One of the triggers of emesis is an excessive serotonin (5-HT) release from enterochromaffin (EC) cells in the intestinal tract, which activates the vomiting center in the brain stem and elicits the vomiting reflex. Here, we propose a 5-HT release assay using human jejunal organoids that are preferentially differentiated into EC cells. In this assay, EC cell-rich organoids were stimulated with emetic risk drugs, and 5-HT release into the media was quantified, along with cellular ATP level and LDH leakage. Anaplastic lymphoma kinase (ALK)\/ROS1 tyrosine kinase inhibitors (TKIs) have been reported to exhibit different probabilities of emesis in clinical settings. We demonstrated that 5-HT release from EC cell-rich organoids could qualitatively distinguish between drugs with high or low emetic risk. The results indicated that 5-HT release by ALK\/ROS1-TKIs tended to occur prior to the onset of LDH leakage from EC cell-rich organoids, suggesting that 5-HT release was not simply a result of cell bursting. Epidermal growth factor receptor TKIs exhibit a lower potency for inducing 5-HT release, which is consistent with their low emetic risk. In summary, the use of EC cell-rich organoids in 5-HT release assays may prove to be a valuable tool in predicting drug-induced emesis in humans during drug development.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae158","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T23:33:29Z","timestamp":1734046409000},"page":"299-312","source":"Crossref","is-referenced-by-count":5,"title":["Development of the serotonin release assay with enterochromaffin cell-rich human intestinal organoids for the risk evaluation of drug-induced emesis"],"prefix":"10.1093","volume":"206","author":[{"given":"Yoshiki","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Maeda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo 113-0033,","place":["Japan"]},{"name":"Laboratory of Pharmaceutics, School of Pharmacy, Kitasato University , Tokyo 108-8641,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba , Ibaraki 305-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba , Ibaraki 305-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba , Ibaraki 305-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba , Ibaraki 305-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kusuhara","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"2025081219530283300_kfae158-B1","doi-asserted-by":"crossref","first-page":"E7632","DOI":"10.1073\/pnas.1804938115","article-title":"A population of gut epithelial 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