Distribution, properties, and inhibitor sensitivity of zebrafish catechol-O-methyl transferases (COMT)

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Semenova , S , Rozov , S & Panula , P 2017 , ' Distribution, properties, and inhibitor sensitivity of zebrafish catechol-O-methyl transferases (COMT) ' , Biochemical Pharmacology , vol. 145 , pp. 147-157 . https://doi.org/10.1016/j.bcp.2017.08.017

Title: Distribution, properties, and inhibitor sensitivity of zebrafish catechol-O-methyl transferases (COMT)
Author: Semenova, Svetlana; Rozov, Stanislav; Panula, Pertti
Contributor: University of Helsinki, Medicum
University of Helsinki, Neuroscience Center
University of Helsinki, Medicum
Date: 2017-12-01
Language: eng
Number of pages: 11
Belongs to series: Biochemical Pharmacology
ISSN: 0006-2952
URI: http://hdl.handle.net/10138/298157
Abstract: Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is an enzyme with multiple functions in vertebrates. COMT methylates and thus inactivates catecholamine neurotransmitters and metabolizes xenobiotic catechols. Gene polymorphism rs4680 that influences the enzymatic activity of COMT affects cognition and behavior in humans. The zebrafish is widely used as an experimental animal in many areas of biomedical research, but most aspects of COMT function in this species have remained uncharacterized. We hypothesized that both comt genes play essential roles in zebrafish. Both comt-a and comt-b were widely expressed in zebrafish tissues, but their relative abundance varied considerably. Homogenates of zebra fish organs, including the brain, showed enzymatic COMT activity that was the highest in the liver and kidney. Treatment of larval zebrafish with the COMT inhibitor Ro41-0960 shifted the balance of catecholamine metabolic pathways towards increased oxidative metabolism. Whole-body concentrations of dioxyphenylacetic acid (DOPAC), a product of dopamine oxidation, were increased in the inhibitor treated larvae, although the dopamine levels were unchanged. Thus, COMT is likely to participate in the processing of catecholamine neurotransmitters in the zebrafish, but the inhibition of COMT in larval fish is compensated efficiently and does not have pronounced effects on dopamine levels. (C) 2017 Elsevier Inc. All rights reserved.
Subject: COMT
Zebrafish
Enzyme activity
Dopamine
Brain
Gut
DEFICIENT MICE
DANIO-RERIO
MONOAMINE-OXIDASE
METHYLTRANSFERASE COMT
LIQUID-CHROMATOGRAPHY
REGIONAL-DISTRIBUTION
PREFRONTAL CORTEX
RELEASED DOPAMINE
MESSENGER-RNA
HUMAN BRAIN
317 Pharmacy
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