Wang C C
Biochim Biophys Acta. 1975 Aug 11;396(2):210-9. doi: 10.1016/0005-2728(75)90035-3.
Intact but fragile mitochondria were isolated from unsporulated oocysts of Eimeria tenella. The mitochondria respired in response to succinate, malate plus pyruvate, and L-ascorbate at rates of 1.00, 0.40, and 0.25 mu1 O2/min/mg protein, respectively. Spectrophotometric analyses of the cytochromes in mitochondria and whole oocysts revealed b-type and o-type cytochromes, at roughly similar levels, but no cytochrome c could be detected. The mitochondrial respiration was inhibited by cyanide, azide, carbon monoxide, antimycin A, and 2-heptyl-4-hydroxyquinoline-N-oxide, but was relatively resistant to rotenone and amytal. The quinolone coccidiostats buquinolate, amquinate, methyl benzoquate, and decoquinate were identified as very powerful inhibitiors of succinate and malate plus pyruvate supported respiration in E. tenella mitochondria. None of these four drugs exhibited any inhibitory effect on chicken liver mitochondria. Only 3 pmol of the quinolones per mg mitochondrial protein was needed to achieve 50% inhibition. The inhibition could not be reversed by coenzymes Q6 or Q10. Since the quinolones did not affect L-ascorbate-supported respiration or the activities of submitochondrial succinate dehydrogenase and NADH dehydrogenase, the site of action of the quinolone coccidiostats was tentatively identified as probably near cytochrome b in E. tenella mitochondria. Mitochondria isolated from an E. tenella amquinate-resistant mutant were much less susceptible to quinolone coccidiostats; 50% inhibition was attained by 300 pmol of the drugs/mg mitochondrial protein. The results suggest that the mechanisms of action of quinolone coccidiostats is by inhibiting the cytochrome-mediated electron transport in the mitochondria of coccidia. 2-Hydroxynaphthoquinone coccidiostats were identified as inhibitors of mitochondrial respiration of both E. tenella and chicken liver. They inhibited submitochondrial succinate dehydrogenase and NADH dehydrogenase of E. tenella, and remained equally active against the mitochondrial function of E. tenella amquinolate-resistant mutant.
从柔嫩艾美耳球虫未孢子化卵囊中分离出完整但脆弱的线粒体。这些线粒体对琥珀酸、苹果酸加丙酮酸以及L-抗坏血酸的呼吸反应速率分别为1.00、0.40和0.25 μl O₂/分钟/毫克蛋白质。对线粒体和整个卵囊中的细胞色素进行分光光度分析，发现存在大致相似水平的b型和o型细胞色素，但未检测到细胞色素c。线粒体呼吸受到氰化物、叠氮化物、一氧化碳、抗霉素A和2-庚基-4-羟基喹啉-N-氧化物的抑制，但对鱼藤酮和戊巴比妥相对耐药。喹诺酮类抗球虫药布喹酯、氨喹酯、甲基苄喹酯和地考喹酯被确定为柔嫩艾美耳球虫线粒体中琥珀酸以及苹果酸加丙酮酸支持的呼吸的非常强大的抑制剂。这四种药物对鸡肝线粒体均未表现出任何抑制作用。每毫克线粒体蛋白质仅需3皮摩尔喹诺酮即可达到50%的抑制率。辅酶Q6或Q10无法逆转这种抑制作用。由于喹诺酮类药物不影响L-抗坏血酸支持的呼吸或线粒体亚基琥珀酸脱氢酶和NADH脱氢酶的活性，喹诺酮类抗球虫药的作用位点初步确定可能在柔嫩艾美耳球虫线粒体中的细胞色素b附近。从对氨喹酯耐药的柔嫩艾美耳球虫突变体中分离出的线粒体对喹诺酮类抗球虫药的敏感性要低得多；每毫克线粒体蛋白质300皮摩尔的药物可达到50%的抑制率。结果表明，喹诺酮类抗球虫药的作用机制是抑制球虫线粒体中细胞色素介导的电子传递。2-羟基萘醌类抗球虫药被确定为柔嫩艾美耳球虫和鸡肝线粒体呼吸的抑制剂。它们抑制柔嫩艾美耳球虫的线粒体亚基琥珀酸脱氢酶和NADH脱氢酶，并且对氨喹酯耐药的柔嫩艾美耳球虫突变体的线粒体功能仍然具有同等活性。
