Semicarbazide-sensitive amine oxidase (SSAO) of the rat aorta. Interactions with some naturally occurring amines and their structural analogues.

The influence of a number of naturally occurring amines and their structural analogues has been examined on the metabolism of radiolabelled benzylamine (BZ) by the membrane bound semicarbazide-sensitive amine oxidase (SSAO) of the rat aorta. Only primary monoamines were effective in reducing the deamination of BZ. In the phenylethylamine series, addition of hydroxyl groups to the benzene ring decreased their potency as inhibitors while addition of a hydroxyl group at the beta position increased the inhibitory potency. Stereoselectivity of action was shown with octopamine, the L-isomer being the more active form. Kinetic analysis of these interactions showed predominantly competitive inhibition and kynuramine had the lowest Ki of 5.4 microM. The aliphatic monoamines, isoamylamine and isobutylamine both competed with BZ. 5-Hydroxytryptamine (5-HT) was the only amine that inhibited non-competitively. Direct evidence for metabolism by SSAO of some of the competing amines such as isoamylamine, phenylethylamine, tyramine and tryptamine was obtained by fluorimetric or radiochemical assays. The inhibitors clorgyline and (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine (MDL 72145) were used to characterise the amine oxidase activity responsible for the deamination. Octopamine and phenylethanolamine (PeOH) were not SSAO substrates and inhibited BZ metabolism in the fluorimetric assay. It is possible that the activity of SSAO is controlled by octopamine released from sympathetic nerve endings or 5-HT released from platelets.