Steinberg P, Acevedo C, Masana M I, Rubio M C
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Apr;337(4):392-6. doi: 10.1007/BF00169529.
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.
研究了去甲肾上腺素代谢和摄取抑制剂对离体大鼠肝脏从灌注液中去除³H-去甲肾上腺素的影响。用3 nmol/l的³H-去甲肾上腺素灌注肝脏，并测定流出液、肝脏和胆汁中的³H-去甲肾上腺素及³H-代谢产物。在90分钟内以14,900±920 dpm·g⁻¹·min⁻¹的速率灌注后，氚的累积去除量为323,574±63,103 dpm/g。灌注90分钟后从肝脏中回收的³H-代谢产物占总代谢产物形成量的71.1±9.0%。仅OMDA部分出现在灌注液中；其流出达到稳态的过程缓慢。抑制MAO或COMT既不改变氚的总去除量，也不改变从肝脏中回收的³H-代谢产物量。可卡因（10 μmol/l）减少了³H-去甲肾上腺素在肝脏中的蓄积。摄取2抑制剂皮质酮（30 μmol/l）减少了氚的总去除量以及从肝脏中回收的³H-代谢产物量，而不改变³H-去甲肾上腺素的蓄积。讨论了存在两个不同区室的假说，一个负责胺的代谢，另一个负责胺的蓄积。
