TY - JOUR T1 - Effect of <em>S</em>-Adenosylhomocysteine and <em>S</em>-Tubercidinylhomocysteine on Catecholamine Methylation in Neuroblastoma Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 368 LP - 373 VL - 13 IS - 2 AU - ROBERT J. MICHELOT AU - NADINE LESKO AU - RICHARD W. STOUT AU - JAMES K. COWARD Y1 - 1977/03/01 UR - http://molpharm.aspetjournals.org/content/13/2/368.abstract N2 - Methylation of dopamine in neuroblastoma cells was studied by measuring the formation of [3H]3-methoxytyramine from [3H]dopamine. Analyses of the cellular extracts by high-pressure liquid chromatography afforded a means of monitoring cellular dopamine metabolism. S-Adenosylhomocysteine and the 7-deaza analogue, S-tubercidinylhomocysteine, both known to inhibit catechol O-methyltransferase in vitro, were used to block the methylation of dopamine in these cells. Both drugs inhibited the formation of 3-methoxytyramine, with an accompanying increase in the synthesis of a material tentatively identified as dopamine 3-sulfate. In this work and in previous work on tRNA methylation in phytohemagglutinin-stimulated rat lymphocytes [(1975) Mol. Pharmacol., 11, 701-707], the 7-deaza analogue was consistently more effective than the natural product inhibitor, S-adenosylhomocysteine. These results are discussed in terms of possible differences in transport and/or metabolism of the drugs. ACKNOWLEDGMENT We thank Dr. Xandra Breakefield for many stimulating and informative discussions regarding the maintenance and use of neuroblastoma cells, and for supplying us with starter cultures of the N-18 and N1E-115 TG6 cell lines. ER -