Summary
The O-methyl derivative methoxytyrosine accumulated rapidly in rat liver after an intraperitoneal injection of l-dopa (50 mg/kg) in combination with 3-hydroxybenzylhydrazine, an inhibitor of the aromatic amino acid decarboxylase. Methoxytyrosine levels reached a plateau 40–60 min after an i.p. injection of l-dopa, of which the tissue concentration declined monoexponentially. Injection of various doses of l-dopa revealed that methoxytyrosine formation was saturable and followed enzyme kinetics in rat liver. The catechol-O-methyltransferase inhibitors pyrogallol, tropolone and α-propyldopacetamide as well as the inhibitor of the aromatic amino acid decarboxylase benserazide inhibited the formation of methoxytyrosine dose-dependently and concomitantly increased the tissue concentration of dopa.
The accumulation of methoxytyrosine from exogeneously applied l-dopa appears to be a reliable indicator of the in vivo activity of catechol-O-methyltransferase.
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Axelrod, J., Albers, W., Clemente, C. D.: Distribution of catechol-O-methyl transferase in the nervous system and other tissues. J. Neurochem. 5, 68–72 (1959)
Axelrod, J., Laroche, M. J.: Inhibition of O-methylation of epinephrine and norepinephrine in vitro and in vivo. Science 130, 800 (1959)
Baldessarini, R. J., Greiner, E.: Inhibition of catechol-O-methyl transferase by catechols and polyphenols. Biochem. Pharmacol. 22, 247–256 (1973)
Bartholini, G., Pletscher, A.: Demethylation of L-3-methoxytyrosine in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 404–409 (1972)
Bartholini, G., Lloyd, K. G., Pletscher, A.: Regional distribution of catecholamines in rat brain after l-3-O-methyldopa and l-dopa. Life Sci. 14, 323–328 (1974)
Belleau, B., Burba, J.: Tropolones: a unique class of potent noncompetitive inhibitors of S-adenosylmethionine-catechol-methyl transferase. Biochim. Biophys. Acta 54, 195–196 (1961)
Broch, O. J.: The in vivo effect of tropolone on noradrenaline metabolism and catechol-O-methyl transferase activity in tissues of the rat. Acta Pharmacol. Toxicol. 33, 417–428 (1973)
Carlsson, A., Lindqvist, M., Fila-Hromadko, S., Corrodi, H.: Synthese von Catechol-O-methyl-transferase-hemmenden Verbindungen — In den Catecholaminmetabolismus eingreifende Substanzen. Helv. Chim. Acta XLV, 270–276 (1962)
Carlsson, A., Waldeck, B.: On the role of the liver catechol-O-methyl-transferase in the metabolism of circulating catecholamines. Acta Pharmacol. Toxicol. (Kbh.) 20, 47–55 (1963)
Crout, J. R.: Inhibition of catechol-O-methyl transferase by pyrogallol in the rat. Biochem. Pharmacol. 6, 47–54 (1961)
Fahn, S., Prasad, A. L. N., Delesie, R.: A reliable and simple method for simultaneous determination of dopa and 3-O-methyldopa in plasma and brain. Anal. Biochem. 46, 557–575 (1972)
Guldberg, H. C., Marsden, C. A.: Catechol-O-methyl transferase: Pharmacological aspects and physiological role. Pharmacol. Rev. 27, 135–206 (1975)
Kehr, W.: Influence of l-3-methoxytyrosine on monoamine synthesis in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 347–356 (1975)
Kehr, W., Carlsson, A., Lindqvist, M.: A method for the determination of 3,4-dihydroxyphenylalanine (Dopa) in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 273–280 (1972)
Kehr, W., Zimmermann, R., Thiede, M.: Methoxytyrosine formation as an indicator of catechol-O-methyltransferase activity in rats in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 287, Suppl.: R1 (1975)
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Kehr, W., Zimmermann, R. & Thiede, M. Methoxytyrosine formation as an indicator of catechol-O-methyltransferase activity in rat liver in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 19–23 (1977). https://doi.org/10.1007/BF00505075
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DOI: https://doi.org/10.1007/BF00505075