Pinto J E, Politi P M, Fernandez B
Institute of Physiology, School of Medicine, University of Buenos Aires, Argentina.
Arch Int Pharmacodyn Ther. 1987 Sep;289(1):140-8.
We have studied the effects of the anthracycline doxorubicin on the release of catecholamines from the perfused bovine adrenal gland. Doxorubicin produced different concentration-dependent effects on adrenomedullary catecholamine secretion. At a 3 x 10(-6) M concentration, doxorubicin facilitated the secretory response induced by acetylcholine and 56 mM K+ but did not affect the spontaneous catecholamine output or that evoked by NaCl deprivation. Conversely, a higher concentration of doxorubicin (10(-4) M) resulted in a significant and irreversible inhibition of the spontaneous secretion of catecholamines, as well as of that caused by acetylcholine or high K+. Doxorubicin at this high concentration did not modify the catecholamine release induced by NaCl deprivation. These results suggest that doxorubicin effects could be mediated at the plasma membrane of the chromaffin cells. The present study is compatible with the idea that increased adrenomedullary catecholamine release is involved in the cardiotoxic action of relatively low doses of doxorubicin.
我们研究了蒽环类药物阿霉素对灌注牛肾上腺释放儿茶酚胺的影响。阿霉素对肾上腺髓质儿茶酚胺分泌产生了不同的浓度依赖性效应。在3×10⁻⁶ M浓度时，阿霉素促进了由乙酰胆碱和56 mM K⁺诱导的分泌反应，但不影响自发儿茶酚胺输出或由NaCl缺乏引起的儿茶酚胺输出。相反，较高浓度的阿霉素（10⁻⁴ M）导致儿茶酚胺自发分泌以及由乙酰胆碱或高钾引起的分泌显著且不可逆地受到抑制。这种高浓度的阿霉素不会改变由NaCl缺乏诱导的儿茶酚胺释放。这些结果表明，阿霉素的作用可能在嗜铬细胞膜上介导。本研究与以下观点一致，即相对低剂量的阿霉素的心脏毒性作用涉及肾上腺髓质儿茶酚胺释放增加。
