Molecular Pharmacology, Vol 13, 368-373, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Effect of S-Adenosylhomocysteine and S-Tubercidinylhomocysteine on Catecholamine Methylation in Neuroblastoma Cells

¹ Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

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.

Note:
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.