Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine
The role of nitric oxide (NO) in the changes in enterochromaffin cells and ileal 5-hydroxytryptamine (5-HT) content induced by a single i.p. administration of methotrexate was investigated in rats. Methotrexate significantly increased inducible NO synthase (iNOS) mRNA and protein expressions in the...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319357032 |
| _version_ | 1818039442451988480 |
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| author | Yuho Takano Megumi Hirano Takuji Machida Yusuke Obara Naoya Hamaue Kana Fujita Masafumi Taniguchi Tomoko Endo Saki Shiga Maiko Machida Kenji Iizuka Masahiko Hirafuji |
| author_facet | Yuho Takano Megumi Hirano Takuji Machida Yusuke Obara Naoya Hamaue Kana Fujita Masafumi Taniguchi Tomoko Endo Saki Shiga Maiko Machida Kenji Iizuka Masahiko Hirafuji |
| author_sort | Yuho Takano |
| collection | DOAJ |
| description | The role of nitric oxide (NO) in the changes in enterochromaffin cells and ileal 5-hydroxytryptamine (5-HT) content induced by a single i.p. administration of methotrexate was investigated in rats. Methotrexate significantly increased inducible NO synthase (iNOS) mRNA and protein expressions in the intestinal tissue at 96 h. Methotrexate also significantly caused hyperplasia of the enterochromaffin cells at 96 h; this was associated with a significant increase in 5-HT content. The methotrexate-induced hyperplasia of enterochromaffin cells and increase in 5-HT content were, however, completely suppressed by daily treatment with dexamethasone, and with NG-nitro-l-arginine methyl ester (l-NAME); this was not observed when meloxicam was administered. Histological examination showed slight but not pronounced mucosal injury, at 96 h after methotrexate administration. The methotrexate-induced decrease in body weight did not fully recover to the control level up to 96 h; however, the methotrexate-induced decrease in food/water intake slightly returned to the control level up to 96 h. l-NAME had no significant effect on methotrexate-induced body weight loss and anorexia. To conclude, the present study suggests that NO derived from methotrexate-induced iNOS plays a critical role in the mechanism of hyperplasia of enterochromaffin cells containing 5-HT in the intestinal tissue of rats. Keywords: Methotrexate, 5-Hydroxytryptamine, Enterochromaffin cells, Nitric oxide, Inducible nitric oxide synthase |
| first_indexed | 2024-12-10T07:58:42Z |
| format | Article |
| id | doaj.art-8e6e6e49918c4b7f8ed07d7fa3063e81 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T07:58:42Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-8e6e6e49918c4b7f8ed07d7fa3063e812022-12-22T01:56:51ZengElsevierJournal of Pharmacological Sciences1347-86132019-09-0114113240Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestineYuho Takano0Megumi Hirano1Takuji Machida2Yusuke Obara3Naoya Hamaue4Kana Fujita5Masafumi Taniguchi6Tomoko Endo7Saki Shiga8Maiko Machida9Kenji Iizuka10Masahiko Hirafuji11Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDivision of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido 006-8590, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan; Corresponding author. School of Health Sciences, Iryo Sosei University, Iwaki, Fukushima 970-8551, Japan.The role of nitric oxide (NO) in the changes in enterochromaffin cells and ileal 5-hydroxytryptamine (5-HT) content induced by a single i.p. administration of methotrexate was investigated in rats. Methotrexate significantly increased inducible NO synthase (iNOS) mRNA and protein expressions in the intestinal tissue at 96 h. Methotrexate also significantly caused hyperplasia of the enterochromaffin cells at 96 h; this was associated with a significant increase in 5-HT content. The methotrexate-induced hyperplasia of enterochromaffin cells and increase in 5-HT content were, however, completely suppressed by daily treatment with dexamethasone, and with NG-nitro-l-arginine methyl ester (l-NAME); this was not observed when meloxicam was administered. Histological examination showed slight but not pronounced mucosal injury, at 96 h after methotrexate administration. The methotrexate-induced decrease in body weight did not fully recover to the control level up to 96 h; however, the methotrexate-induced decrease in food/water intake slightly returned to the control level up to 96 h. l-NAME had no significant effect on methotrexate-induced body weight loss and anorexia. To conclude, the present study suggests that NO derived from methotrexate-induced iNOS plays a critical role in the mechanism of hyperplasia of enterochromaffin cells containing 5-HT in the intestinal tissue of rats. Keywords: Methotrexate, 5-Hydroxytryptamine, Enterochromaffin cells, Nitric oxide, Inducible nitric oxide synthasehttp://www.sciencedirect.com/science/article/pii/S1347861319357032 |
| spellingShingle | Yuho Takano Megumi Hirano Takuji Machida Yusuke Obara Naoya Hamaue Kana Fujita Masafumi Taniguchi Tomoko Endo Saki Shiga Maiko Machida Kenji Iizuka Masahiko Hirafuji Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine Journal of Pharmacological Sciences |
| title | Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine |
| title_full | Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine |
| title_fullStr | Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine |
| title_full_unstemmed | Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine |
| title_short | Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine |
| title_sort | nitric oxide plays a critical role in methotrexate induced hyperplasia of enterochromaffin cells containing 5 hydroxytryptamine in rat small intestine |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319357032 |
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