THE ROLE OF MAO-A AND MAO-B IN THE METABOLIC-DEGRADATION OF NORADRENALINE IN HUMAN ARTERIES

1 Segments of human cystic, gastric and ileocolic arteries were obtain ed from patients undergoing surgery. 2 Segments of arterial tissues, t he noradrenaline content of which ranged between 0.27 and 0.52 mu g g( -1), were incubated with 0.1 mu mol l(-1)[H-3]-noradrenaline for 30 mi n and the accumulation of the amine as well as the formation of metabo lites was measured. 3 In all the arteries, oxidative deamination predo minated over O-methylation; the mean values of the deaminated and O-me thylated metabolites formed for the three arteries were 247.6 and 82.4 pmol g(-1) tissue, respectively. Dihydroxymandelic acid (DOMA) was th e most abundant metabolite. 4 Both clorgyline (a selective MAO-A inhib itor) and selegiline (a selective MAO-B inhibitor) reduced the formati on of dihydroxyphenylglycol (DOPEG), DOMA and O-methylated-deaminated metabolites (OMDA), and increased that of normetanephrine (NMN). Howev er, clorgyline depressed the formation of DOPEG more than that of DOMA , while selegiline depressed the formation of DOMA more than that of D OPEG. 5 In conclusion, three major differences distinguish the metabol ism of noradrenaline by human arteries from that observed in other spe cies: (1) the large predominance of deamination over O-methylation; (2 ) the extremely high formation of DOMA; and (3) the relative lack of s electivity of clorgyline and selegiline for MAO-A and B, respectively. Since the arterial vessels used were collected from patients older th an 60 years, the morphological changes depending on age may explain th e increase in DOMA formation.