The uptake and metabolism of 3H-catecholamines in rat cerebral cortex slices

Summary The accumulation and metabolism of ³H-catecholamines were studied in cerebral cortex slices obtained from rats pretreated with reserpine, during 30 min of incubation with 50 nmol/l of the ³H-amines. In some experiments neuronal uptake (uptake,) was inhibited by the presence of 0.3 mol/l desipramine, in others COMT was inhibited by 30 mol/l U-0521. When both MAO and COMT were intact, most of the metabolism of ³H-noradrenaline was neuronal (i. e., desipramine-sensitive). For ³H-adrenaline rates of neuronal metabolism were much lower than for ³H-noradrenaline, non-neuronal O-methylation accounting for about 50% of total metabolism. Rates of metabolism of ³H-dopamine were similar to those of ³H-noradrenaline, but with a predominance of non-neuronal metabolism, which involved O-methylation and deamination. Under these conditions, very little ³H-catecholamine was recovered from the tissues; moreover, desipramine tended to increase tissue levels. Hence, tissue content then appears to partly reflect extracellularly distributed ³H-amines. After block of MAO rates of metabolism of ³H-noradrenaline and ³H-dopamine were greatly reduced, and tissue levels were increased. Desipramine now antagonized the accumulation of ³H-amines in the tissue, while U-0521 increased it. Rates of O-methylation (in the presence of desipramine) increased in the order ³H-noradrenaline < ³H-dopamine. It is concluded that neuronal uptake is associated with MAO only, and rates of neuronal deamination increased in the order: ³H-adrenaline < ³H-dopamine « ³H-noradrenaline. Non-neuronal uptake is associated with both, COMT and MAO, and rates of non-neuronal metabolism increased in the order: ³H-adrenaline < ³H-noradrenaline « ³H-dopamine.Abbreviations COMT catechol-O-methyl transferase - DOMA dihydroxymandelic acid - DOPAC dihydroxyphenylacetic acid - DOPEG dihydroxyphenylglycol - DOPET dihydroxyphenylethanol - HVA homovanillic acid - MAO monoamine oxidase - MN metanephrine - MOPEG methoxyhydroxyphenylglycol - MOPET methoxyhydroxyphenylethanol - NMN normetanephrine - 3-OMT 3-O-methyl-tyramine - VMA vanillylmandelic acid Supported by the Deutsche Forschungsgemeinschaft (SFB 176) Send offprint requests to U. Trendelenburg at the above addresswith the technical assistance of M. Babl