Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

2961249

Reference Type

Journal Article

Title

Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion

Author(s)

Kon, R; Ikarashi, N; Hayakawa, A; Haga, Y; Fueki, A; Kusunoki, Y; Tajima, M; Ochiai, W; Machida, Y; Sugiyama, K

Year

2015

Is Peer Reviewed?

Journal

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929

Volume

145

Issue

Page Numbers

337-347

Language

English

PMID

25766885

DOI

10.1093/toxsci/kfv055

Web of Science Id

WOS:000355663300011

Abstract

Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the colon, where it plays a critical role in the regulation of fecal water content. This study investigated the role of AQP3 in the colon in morphine-induced constipation. AQP3 expression levels in the colon were analyzed after oral morphine administration to rats. The degree of constipation was analyzed after the combined administration of HgCl2 (AQP3 inhibitor) or fluoxetine (5-HT reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression levels in rat colon were increased during morphine-induced constipation. The combination of HgCl2 and morphine improved morphine-induced constipation. Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5-HT treatment significantly increased the AQP3 expression level and the nuclear translocation of peroxisome proliferator-activated receptor gamma (PPAR gamma) 1 h after treatment. Pretreatment with fluoxetine significantly suppressed these increases. Fluoxetine pretreatment suppressed the development of morphine-induced constipation and the associated increase in AQP3 expression in the colon. The results suggest that morphine increases the AQP3 expression level in the colon, which promotes water absorption from the luminal side to the vascular side and causes constipation. This study also showed that morphine-induced 5-HT secreted from the colon was taken into cells by SERT and activated PPAR gamma, which subsequently increased AQP3 expression levels.

Keywords

aquaporin-3; morphine; constipation; serotonin; fluoxetine