Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine.

Autor:	Takano Y; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Hirano M; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Machida T; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Obara Y; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Hamaue N; Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Fujita K; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Taniguchi M; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Endo T; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Shiga S; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Machida M; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido 006-8590, Japan., Iizuka K; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan., Hirafuji M; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. Electronic address: masahiko.hirafuji@isu.ac.jp.
Jazyk:	angličtina
Zdroj:	Journal of pharmacological sciences [J Pharmacol Sci] 2019 Sep; Vol. 141 (1), pp. 32-40. Date of Electronic Publication: 2019 Sep 10.
DOI:	10.1016/j.jphs.2019.09.001
Abstrakt:	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 N G -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. (Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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