title: Methotrexate causes a change in intestinal 5-hydroxytryptamine metabolism in rats.
abstract: The effects of methotrexate on 5-hydroxytryptamine (5-HT) metabolism in the intestinal tissue of rats were investigated during the delayed phase after a single administration. Rats were i.p. injected with methotrexate or with saline as a control, and kaolin and food intakes were measured by an automatic monitoring apparatus. At 96 h after administration, dissected-out ileal tissue was frozen rapidly in liquid nitrogen for further analysis or fixed for immunohistochemical staining. Methotrexate at a dose of 50 mg/kg caused a time-dependent increase in kaolin intake lasting up to 72 h after administration, which returned to the control level at 96 h after administration. This dose of methotrexate caused a gradual decrease in body weight, food intake, and water intake lasting up to 72 h, which approached the control level at 96 h. Methotrexate caused pathologic changes, including a moderate inflammatory response in the ileal tissue and an increase in the number of L-tryptophan hydroxylase (TPH)-expressing cells in the ileal mucosa. Methotrexate also caused a significant increase in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content and in TPH1 mRNA expression in the ileal tissues. It had no significant effects on mRNA expression of serotonin transporter, COX-1, or COX-2 or on myeloperoxidase activity. This study demonstrated, for the first time, that methotrexate caused a change in the ileal 5-HT metabolism associated with hyperplasia of mucosal enterochromaffin cells.
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Yuho
authors: Y
authors: Takano
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Takuji
authors: T
authors: Machida
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Yusuke
authors: Y
authors: Obara
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Megumi
authors: M
authors: Hirano
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Sae
authors: S
authors: Kudo
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Minako
authors: M
authors: Takagi
authors: Departments of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Naoya
authors: N
authors: Hamaue
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Kenji
authors: K
authors: Iizuka
authors: Departments of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. Electronic address: hirafuji@hoku-iryo-u.ac.jp.
authors: Masahiko
authors: M
authors: Hirafuji
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004435:Eating / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007616:Kaolin / Q000008:administration & dosage; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008727:Methotrexate / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; D007616:Kaolin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009195:Peroxidase; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D008727:Methotrexate
keywords: 5-hydroxytryptamine (5-HT); COX; Enterochromaffin cells; Methotrexate; Methotrexate (PubChem CID: 126941); l-tryptophan hydroxylase (TPH)