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

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 (uptake1) was inhibited by the presence of 0.3 mumol/l desipramine, in others COMT was inhibited by 30 mumol/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 less than 3H-dopamine. It is concluded that neuronal uptake is associated with MAO only, and rates of neuronal deamination increased in the order: 3H-adrenaline less than 3H-dopamine much less than 3H-noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)