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)
Trendelenburg
U
U
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology
D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D011427:Propiophenones; C006104:U 0521; D012110:Reserpine; D010293:Pargyline; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine