Role of Nitric Oxide in the Change of 5-Hydroxytryptamine Synthesis in the Intestine by a Consecutive Administration of Methotrexate to Rats

Takuji Machida; Akari Inotani; Saki Shiga; Shuto Kon; Takumi Yanada; Hiroya Kobayashi; Naoya Hamaue; Masahiko Hirafuji; Kenji Iizuka

doi:10.1159/000508973

Role of Nitric Oxide in the Change of 5-Hydroxytryptamine Synthesis in the Intestine by a Consecutive Administration of Methotrexate to Rats

Pharmacology. 2020;105(11-12):723-728. doi: 10.1159/000508973. Epub 2020 Jul 21.

Authors

Takuji Machida¹, Akari Inotani², Saki Shiga², Shuto Kon², Takumi Yanada², Hiroya Kobayashi², Naoya Hamaue³, Masahiko Hirafuji², Kenji Iizuka²

Affiliations

¹ Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan, tmachida@hoku-iryo-u.ac.jp.
² Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
³ Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.

PMID: 32694256
DOI: 10.1159/000508973

Abstract

This study aimed to investigate whether the consecutive administration of methotrexate affects 5-hydroxytryptamine (5-HT) synthesis in the rat small intestine. Rats received methotrexate at a dose of 12.5 mg/kg intraperitoneally on 4 consecutive days. NG-nitro-L-arginine methyl ester (L-NAME) was given subcutaneously to inhibit nitric oxide (NO) synthase. Methotrexate moderately altered 5-HT synthesis, whereas the combined administration of methotrexate and L-NAME significantly changed 5-HT synthesis in the rat ileal tissue. These results suggest that endogenous NO has an antagonistic role in the induction of 5-HT synthesis in rats following the consecutive administration of methotrexate.

Keywords: 5-Hydroxytryptamine; Methotrexate; Small intestine; Substance P; Tryptophan hydroxylase.

Publication types

News

MeSH terms

Animals
Drug Administration Schedule
Enzyme Inhibitors / administration & dosage
Enzyme Inhibitors / pharmacology*
Injections, Intraperitoneal
Intestinal Diseases / chemically induced
Intestine, Small / drug effects*
Intestine, Small / metabolism*
Intestine, Small / pathology
Male
Methotrexate / administration & dosage
Methotrexate / pharmacology*
NG-Nitroarginine Methyl Ester / administration & dosage
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors
RNA, Messenger / metabolism
Rats
Rats, Wistar
Serotonin / biosynthesis*
Substance P / drug effects
Substance P / metabolism
Tachykinins / drug effects
Tachykinins / genetics
Tachykinins / metabolism
Tryptophan Hydroxylase / drug effects
Tryptophan Hydroxylase / genetics
Tryptophan Hydroxylase / metabolism

Substances

Enzyme Inhibitors
RNA, Messenger
Tachykinins
Nitric Oxide
Serotonin
Substance P
Nitric Oxide Synthase
Tryptophan Hydroxylase
NG-Nitroarginine Methyl Ester
Methotrexate