Effects of norlaudanosolinecarboxylic acids on enzymes of catecholamine metabolism

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 212; no. 1; pp. 91 - 96
• Main Authors: Coscia, C J, Burke, W J, Galloway, M P, Kosloff, A H, Lasala, J M, McFarlane, J, Mitchell, J S, O'Toole, M M, Roth, B L
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.01.1980
• Subjects: Animals; Aromatic-L-Amino-Acid Decarboxylases - physiology; Biological Assay; Carboxylic Acids - pharmacology; Catechol O-Methyltransferase Inhibitors; Catecholamines - metabolism; Coenzymes - physiology; D-Amino-Acid Oxidase - physiology; Dopamine beta-Hydroxylase - antagonists & inhibitors; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Isoquinolines - pharmacology; Male; Mice; Monoamine Oxidase Inhibitors - pharmacology; Papaverine - analogs & derivatives; Rats; Tetrahydropapaveroline - pharmacology; Transaminases - physiology; Tyrosine 3-Monooxygenase - antagonists & inhibitors
• ISSN: 0022-3565; 1521-0103

Enzymes involved in catecholamine metabolism were assayed in the presence of a new class of naturally occurring tetrahydroisoquinoline alkaloids, the norlaudanosolinecarboxylic acids (NLCAs). NLCAs inhibited tyrosine hydroxylase noncompetitively with respect to its substrate, tyrosine and the cofactor, 6-methyltetrahydropterin (NLCA Kj = 4 x 10(-4) M; 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) Kj = 1.5 x 10(-4) M). Adrenal dopamine-beta-hydroxylase was also inhibited by NLCAs [3'O-methylnorlaudanosolinecarboxylic acid (MNLCA) Kj = 1.2 x 10(-4) M] and NLCA is a competitive inhibitor of norepinephrine methylation by hepatic catechol-O-methyltransferase (NLCA Kj = 5.6 x 10(-5) M). While a slight reduction of rat adrenal monoamine oxidase by MNLCA was also observed, NLCA did not affect the oxidation of tyrosine by D-amino acid oxidase. Kinetic patterns of tyrosine aminotransferase and aromatic amono acid decarboxylase from rat liver were not altered by addition of 1 to 10 x 10(-5) M NLCA or its 3'-O-methyl ether (MNLCA). In vivo studies of brain tyrosine metabolism in mouse neonates corroborated results on the in vitro effect of DNLCA on tyrosine hydroxylase. The potential of high-pressure liquid chromatography was demonstrated in both enzyme assays and radiometric studies of in vivo metabolism.