O-methylation of (+)-(R)- and (-)-(S)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) in the presence of pig brain catechol-O-methyltransferase.
(+)-(R)- and (-)-(S)-salsolinol, dopamine-derived tetrahydroisoquinolines, were tested as substrates of pig brain soluble and membrane-bound catechol-O-methyltransferase (COMT) and as inhibitors of O-methylation of dopamine by soluble COMT in vitro. Methylation products were separated by high-performance liquid chromatography with electrochemical detection. Quantification of the products showed that O-methylation of (+)-(R)-salsolinol by soluble COMT afforded the 7-O-methylated product salsoline preferentially, whereas (-)-(s)-salsolinol yielded almost equivalent amounts of the 6- and 7-methyl ethers. Unlike O-methylation by soluble COMT, 7-O/6-O-methylation ratio produced by membrane-bound COMT varied with (+)-(R)-salsolinol concentration. As to the O-methylation of dopamine by soluble COMT, comparable competitive inhibition was observed with both (+)-(R)- and (-)-(S)-salsolinol.
Hötzl
B K
BK
Department of Physiological Chemistry, University of Ulm, Germany.
Thomas
H
H
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D008745:Methylation; D013237:Stereoisomerism; D013552:Swine
D007546:Isoquinolines; C036617:salsolinol; D002394:Catechol O-Methyltransferase