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Xenobiotica
the fate of foreign compounds in biological systems
Volume 46, 2016 - Issue 7
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General Xenobiochemistry

Species and tissue differences in serotonin glucuronidation

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Pages 605-611 | Received 12 Aug 2015, Accepted 25 Sep 2015, Published online: 02 Nov 2015
 

Abstract

1. Serotonin is a UGT1A6 substrate that is mainly found in the extrahepatic tissues where some UGT1As are expressed. The aim of the present study was to characterize serotonin glucuronidation in various tissues of humans and rodents.

2. Serotonin glucuronidation in the human liver and kidney fitted to the Michaelis–Menten model, and the Km values were similar to that of recombinant UGT1A6. However, serotonin glucuronidation in the human intestine fitted to the Hill equation, indicating that it is likely catalyzed not only by UGT1A6, but also by another UGT1A isoform. Serotonin glucuronidation in the rat liver, intestine and kidney fitted well to the Michaelis–Menten model and exhibited monophasic kinetics in the kidney, but biphasic kinetics in the liver and intestine. Furthermore, serotonin glucuronidation in the rat brain fitted best to the Hill equation. Serotonin glucuronidation in the mouse tissues fitted to the Michaelis–Menten model and exhibited monophasic kinetics in the liver and intestine microsomes, but biphasic kinetics in the kidney and brain microsomes.

3. In conclusion, we clarified that tissue and species differences exist in serotonin glucuronidation. It is necessary to take these potential differences into account when considering the pharmacodynamics and pharmacokinetics of serotonin.

Declaration of interest

This work was supported partly by JSPS KAKENHI Grant Number 25460200. The authors report no declarations of interest.

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