Delayed O-methylation of L-DOPA in MB-COMT-deficient mice after oral administration of L-DOPA and carbidopa

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Tammimäki , A , Aonurm-Helm , A & Männistö , P T 2018 , ' Delayed O-methylation of L-DOPA in MB-COMT-deficient mice after oral administration of L-DOPA and carbidopa ' , Xenobiotica , vol. 48 , no. 4 , pp. 325-331 . https://doi.org/10.1080/00498254.2017.1315781

Title: Delayed O-methylation of L-DOPA in MB-COMT-deficient mice after oral administration of L-DOPA and carbidopa
Author: Tammimäki, Anne; Aonurm-Helm, Anu; Männistö, Pekka T.
Contributor organization: Division of Pharmacology and Pharmacotherapy
Faculty of Pharmacy
Drug Research Program
Date: 2018
Language: eng
Number of pages: 7
Belongs to series: Xenobiotica
ISSN: 0049-8254
DOI: https://doi.org/10.1080/00498254.2017.1315781
URI: http://hdl.handle.net/10138/234481
Abstract: 1.Catechol-O-methyltransferase (COMT) is involved in the O-methylation of l-DOPA, dopamine, and other catechols. The enzyme is expressed in two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-COMT), which is anchored to intracellular membranes. 2.To obtain specific information on the functions of COMT isoforms, we studied how a complete MB-COMT deficiency affects the total COMT activity in the body, peripheral l-DOPA levels, and metabolism after l-DOPA (10mg kg(-1)) plus carbidopa (30mg kg(-1)) administration by gastric tube in wild-type (WT) and MB-COMT-deficient mice. l-DOPA and 3-O-methyl-l-DOPA (3-OMD) levels were assayed in plasma, duodenum, and liver. 3.We showed that the selective lack of MB-COMT did not alter the total COMT activity, COMT enzyme kinetics, l-DOPA levels, or the total O-methylation of l-DOPA but delayed production of 3-OMD in plasma and peripheral tissues.
Subject: COMT isoforms
knock-in mutation
L-DOPA
MB-COMT
metabolism
mouse pharmacokinetics
S-COMT
site-directed mutation
METHYLTRANSFERASE GENE
MESSENGER-RNAS
CATECHOL
CLONING
BRAIN
TRANSFERASE
METABOLISM
EXPRESSION
PROMOTERS
PROTEINS
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc_sa
Usage restriction: openAccess
Self-archived version: acceptedVersion


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