Stringer B K, Harmon H J
Department of Zoology, Oklahoma State University, Stillwater 74078.
Biochem Pharmacol. 1990 Sep 1;40(5):1077-81. doi: 10.1016/0006-2952(90)90496-8.
Dibucaine-HCl inhibited mitochondrial cytochrome c oxidase activity in intact mitochondria with 50% inhibition occurring at 1.1 mM dibucaine-HCl. Dibucaine-HCl did not prevent the reduction of cytochrome oxidase by ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD) when measured at 604 nm but prevented 50% of the absorbance change at 445 nm; dithionite reduced the oxidase completely. Dibucaine prevented binding of CO to oxidase reduced with ascorbate plus TMPD by preventing the reduction of cytochrome a3. The midpotenials of cytochrome c and cytochrome oxidase, the visible absorbance wavelength maxima, and the position and intensity of the signals of the EPR spectrum of the oxidase were not affected. Dibucaine-HCl prevented ascorbate plus TMPD-driven reduction of the near infra-red detectable copper center associated with cytochrome a: dithionite subsequently reduced this center. Dibucaine-HCl inhibited cytochrome oxidase activity by interacting between cytochrome a and its associated copper. Since respiration was 8-fold less sensitive in submitochondrial particles, this site of inhibition is on the cytoplasmic side of the membrane.
盐酸地布卡因抑制完整线粒体中的线粒体细胞色素c氧化酶活性，在1.1 mM盐酸地布卡因时出现50%的抑制。当在604 nm处测量时，盐酸地布卡因并不阻止抗坏血酸加盐酸N,N,N',N'-四甲基对苯二胺（TMPD）对细胞色素氧化酶的还原，但阻止了445 nm处50%的吸光度变化；连二亚硫酸盐可完全还原氧化酶。地布卡因通过阻止细胞色素a3的还原，防止CO与抗坏血酸加TMPD还原的氧化酶结合。细胞色素c和细胞色素氧化酶的中点电位、可见吸光度波长最大值以及氧化酶EPR光谱信号的位置和强度均未受影响。盐酸地布卡因阻止抗坏血酸加TMPD驱动的与细胞色素a相关的近红外可检测铜中心的还原：连二亚硫酸盐随后可还原该中心。盐酸地布卡因通过细胞色素a与其相关铜之间的相互作用抑制细胞色素氧化酶活性。由于亚线粒体颗粒中的呼吸敏感性低8倍，因此该抑制位点位于膜的细胞质侧。
