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 obtained from patients undergoing surgery. 2. Segments of arterial tissues, the noradrenaline content of which ranged between 0.27 and 0.52 microg g(-1), were incubated with 0.1 micromol l(-1) [3H]-noradrenaline for 30 min and the accumulation of the amine as well as the formation of metabolites was measured. 3. In all the arteries, oxidative deamination predominated over O-methylation; the mean values of the deaminated and O-methylated metabolites formed for the three arteries were 247.6 and 82.4 pmol g(-1) tissue, respectively. Dihydroxymandelic acid (DOMA) was the most abundant metabolite. 4. Both clorgyline (a selective MAO-A inhibitor) and selegiline (a selective MAO-B inhibitor) reduced the formation of dihydroxyphenylglycol (DOPEG), DOMA and O-methylated-deaminated metabolites (OMDA), and increased that of normetanephrine (NMN). However, clorgyline depressed the formation of DOPEG more than that of DOMA, while selegiline depressed the formation of DOMA more than that of DOPEG. 5. In conclusion, three major differences distinguish the metabolism of noradrenaline by human arteries from that observed in other species: (1) the large predominance of deamination over O-methylation; (2) the extremely high formation of DOMA; and (3) the relative lack of selectivity of clorgyline and selegiline for MAO-A and B, respectively. Since the arterial vessels used were collected from patients older than 60 years, the morphological changes depending on age may explain the increase in DOMA formation.
Figueiredo
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Laboratory of Pharmacodynamics, Faculty of Pharmacy, University of Coimbra, Portugal.
Caramona
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Paiva
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Guimarães
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D000368:Aged; D001158:Arteries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D006801:Humans; D008333:Mandelic Acids / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D012642:Selegiline / Q000494:pharmacology
D008333:Mandelic Acids; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008734:Methoxyhydroxyphenylglycol; C000989:3,4-dihydroxymandelic acid; D008995:Monoamine Oxidase; D003010:Clorgyline; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine