INHIBITORS OF CATECHOLAMINE METABOLIZING ENZYMES CAUSE CHANGES IN S-ADENOSYLMETHIONINE AND S-ADENOSYLHOMOCYSTEINE IN THE RAT-BRAIN

Previous studies have shown that the biochemical changes that occur in parkinsonism are associated with disturbances in methylation reaction s. Therefore, our hypothesis was that MAO and COMT inhibitors, which i nhibit the metabolism of dopamine, might affect the methylation reacti on. In the present study, we analyzed levels of S-adenosylmethionine ( SAM) and S-adenosylhomocysteine (SAH) in brain homogenates from rats w hich had received a one-week treatment with tolcapone or phenelzine, i nhibitors of COMT and MAO, respectively. Tolcapone treatment caused an increase in the levels of SAM (130% as compared with control animals, p<0.001). In animals treated with phenelzine, the SAM levels were 78% of those of the controls (p<0.05). SAH levels were slightly increased (115% as compared with controls, p<0.05) in the phenelzine group, whi le they were unchanged in the tolcapone treated animals. Treatment wit h tolcapone decreased the catalytic activity of methionine adenosyltra nsferase (MAT) (from 15.4+/-1.6 to 11.3+/-1.4 pmol mg(-1) min(-1), p<0 .0001) while phenelzine treatment had no significant effect. In additi on the transmethylation ratio (SAM/SAH) were significantly increased w ith tolcapone (120%, p<0.05) and decreased with phenelzine (71%, p<0.0 5) as compared to the controls. The essential finding of this paper wa s that brain SAM levels were reduced by MAO inhibition and enhanced by COMT inhibition. (C) 1998 Elsevier Science Ltd. All rights reserved.