Uptake and metabolism of 3H-(+/-)-noradrenaline in the isolated perfused rat liver.
The influence of inhibitors of metabolism and uptake of noradrenaline on the 3H-noradrenaline removal from the perfusion fluid by the isolated rat liver was studied. Livers were perfused with 3 nmol/l 3H-noradrenaline and 3H-noradrenaline and 3H-metabolites were determined in effluent, liver and bile. After the perfusion with 14,900 +/- 920 dpm.g-1.min-1 during 90 min, cumulative removal of tritium was 323,574 +/- 63,103 dpm/g. 3H-metabolites recovered from the liver after 90 min perfusion represented 71.1 +/- 9.0% of total metabolite formation. Only the OMDA-fraction appeared in the perfusate; its approach to steady state of efflux was slow. The inhibition either of MAO or COMT changed neither the total removal of tritium nor the 3H-metabolites recovered from the liver. Cocaine (10 mumol/l) reduced the accumulation of 3H-noradrenaline in the liver. The uptake2 inhibitor corticosterone (30 mumol/l) diminished total removal of tritium and the 3H-metabolites recovered from the liver without changing the accumulation of 3H-noradrenaline. The hypothesis of two different compartments, one responsible for the metabolism and the other for the accumulation of the amine is discussed.
Steinberg
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P
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Acevedo
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C
Masana
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MI
Rubio
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MC
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D065098:Catechol O-Methyltransferase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline; D003042:Cocaine; D003345:Corticosterone; D009638:Norepinephrine