Fliegel L, Takeo S, Beamish R E, Dhalla N S
Can J Cardiol. 1985 Mar;1(2):122-7.
Adrenochrome uptake and its subcellular distribution were examined using isolated perfused rat heart preparation. The heart was perfused for 30 min with a medium containing 1 to 50 mg/l of 14C-adrenochrome and the subcellular fractions were isolated to measure their radioactivities. A decline in contractile force, a rise in resting tension and an increase in adrenochrome uptake by the heart were seen to depend upon the time of perfusion and the concentration of adrenochrome in the medium. The sarcolemmal fraction had the highest uptake of adrenochrome and this was followed by the microsomal fraction; some accumulation of adrenochrome was also observed in the myofibrillar and mitochondrial fractions. Either 10 or 20 min reperfusion of the heart previously exposed to 25 mg/l of adrenochrome, resulted in approximately 50 or 37% of the radioactivity remaining in the heart; this indicates irreversible binding of adrenochrome to the tissue. Reperfusion of the heart showed restoration of the resting tension but the contractile force did not show any recovery. Propranolol and iproniazid, which have been shown to inhibit the adrenochrome induced cardiotoxicity, reduced adrenochrome uptake by the heart, and prevented adrenochrome-induced depression in contractile force and rise in resting tension. These results indicate that adrenochrome is taken up by the heart and induces cardiac disturbances through its action on different subcellular organelles in the myocardium.
利用离体灌注大鼠心脏标本研究了肾上腺色素的摄取及其亚细胞分布。用含有1至50mg/l 14C-肾上腺色素的培养基灌注心脏30分钟，然后分离亚细胞组分以测量其放射性。发现心脏收缩力下降、静息张力升高以及肾上腺色素摄取增加取决于灌注时间和培养基中肾上腺色素的浓度。肌膜组分对肾上腺色素的摄取最高，其次是微粒体组分；在肌原纤维和线粒体组分中也观察到一些肾上腺色素的积累。先前暴露于25mg/l肾上腺色素的心脏再灌注10或20分钟后，心脏中约50%或37%的放射性残留；这表明肾上腺色素与组织发生不可逆结合。心脏再灌注显示静息张力恢复，但收缩力未恢复。已证明能抑制肾上腺色素诱导的心脏毒性的普萘洛尔和异烟肼，可减少心脏对肾上腺色素的摄取，并防止肾上腺色素引起的收缩力降低和静息张力升高。这些结果表明，肾上腺色素被心脏摄取，并通过其对心肌中不同亚细胞器的作用诱发心脏紊乱。
