Effects of norlaudanosolinecarboxylic acids on enzymes of catecholamine metabolism

CJ Coscia, WJ Burke, MP Galloway, AH Kosloff, JM Lasala, J McFarlane, JS Mitchell, MM O'Toole and BL Roth

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.

Volume 212, Issue 1, pp. 91-96, 01/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics

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