On the role of O-methylation in the metabolism of S-adenosylmethionine in rat brain

Abstract

The effects of tropolone and pyrogallol in areas of the rat brain with a high and low density of catecholaminergic innervation, i.e. the striatum and cortex, on S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations were studied and related to the extent of catechol-O-methyltransferase (COMT) inhibition. Moreover, the effects of drugs enhancing dopamine (DA) or noradrenaline (NA) utilization in these areas were also investigated. Pyrogallol reduced the concentrations of SAM in a similar manner in both areas and increased SAH much more in the cortex than in the striatum; these effects corresponded to that on O-methylation in terms of dose-effect relationships, indicating that there is no compartmentation of SAM with respect to the methylation process in which it is used. Tropolone increased SAM and decreased SAH in the striatum only, and these effects occurred at somewhat higher doses than the inhibition of COMT. Together with the data showing that DA antagonists decrease SAM in the striatum, this suggests that a significant proportion of SAM metabolism in this area results from O-methylation of DA (or its deaminated metabolite). A number of antidepressants did not alter the levels of SAM in either area, but some of the drugs increased SAH in the cortex. However, this was not correlated with their effects on the noradrenergic system. Inhibition of the synthesis and decarboxylation of SAM by cycloleucine and methylglyoxal bis(guanylhydrazone) (MGBG), respectively, did not cause the expected pattern of changes, i.e. decreases of both SAM and SAH in the former case and either increase or no change in both parameters in the latter. Instead, both cycloleucine and MGBG increased SAH while decreasing SAM, suggesting an involvement of other properties of these drugs.