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 μmol/l desipramine, in others COMT was inhibited by 30 μmol/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.
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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
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Supported by the Deutsche Forschungsgemeinschaft (SFB 176)
Send offprint requests to U. Trendelenburg at the above address
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Trendelenburg, U. The uptake and metabolism of 3H-catecholamines in rat cerebral cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 339, 293–297 (1989). https://doi.org/10.1007/BF00173580
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DOI: https://doi.org/10.1007/BF00173580