Tammimäki Anne, Aonurm-Helm Anu, Männistö Pekka T
a Division of Pharmacology and Pharmacotherapy , Faculty of Pharmacy, University of Helsinki , Finland and.
b Division of Pharmacology and Toxicology , Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu , Tartu , Estonia.
Xenobiotica. 2018 Apr;48(4):325-331. doi: 10.1080/00498254.2017.1315781. Epub 2017 Apr 21.
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) plus carbidopa (30 mg kg) 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.
