title: Delayed O-methylation of l-DOPA in MB-COMT-deficient mice after oral administration of l-DOPA and carbidopa.
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 (10 mg kg-1) plus carbidopa (30 mg 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.
authors.affiliation: a Division of Pharmacology and Pharmacotherapy , Faculty of Pharmacy, University of Helsinki , Finland and.
authors.forename: Anne
authors.initials: A
authors.lastname: Tammimäki
authors.affiliation: b Division of Pharmacology and Toxicology , Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu , Tartu , Estonia.
authors.forename: Anu
authors.initials: A
authors.lastname: Aonurm-Helm
authors.affiliation: a Division of Pharmacology and Pharmacotherapy , Faculty of Pharmacy, University of Helsinki , Finland and.
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Männistö
mesh_terms: D000818:Animals; D002230:Carbidopa / Q000493:pharmacokinetics / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D007980:Levodopa / Q000493:pharmacokinetics / Q000494:pharmacology; D008745:Methylation; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D007980:Levodopa; D002394:Catechol O-Methyltransferase; D002230:Carbidopa
keywords: COMT isoforms; MB-COMT; S-COMT; knock-in mutation; l-DOPA; metabolism; mouse pharmacokinetics; site-directed mutation