Harada K, Endo Y, Warashina A, Inoue M
Department of Cell and Systems Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan.
Department of Cell and Systems Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan.
Neuroscience. 2015 Aug 20;301:134-43. doi: 10.1016/j.neuroscience.2015.05.080. Epub 2015 Jun 3.
The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized.
在线粒体抑制剂(CN⁻,一种复合体IV抑制剂;以及CCCP,质子载体)对大鼠和豚鼠肾上腺嗜铬细胞儿茶酚胺(CA)分泌及线粒体功能的影响方面,进行了功能和生化研究。豚鼠嗜铬细胞对CN⁻或CCCP有明显的CA分泌反应,但大鼠细胞对二者几乎没有分泌反应。大鼠肾上腺髓质的静息代谢率与豚鼠肾上腺髓质的静息代谢率无差异。另一方面,豚鼠嗜铬细胞对CN⁻的线粒体膜电位(ΔΨm)去极化时间进程比大鼠嗜铬细胞慢,且这种差异被F1F0 - ATP酶抑制剂寡霉素消除。使用Mg²⁺指示剂间接测量,CCCP诱导的豚鼠嗜铬细胞内ATP降低程度小于大鼠嗜铬细胞。豚鼠肾上腺髓质中F1F0 - ATP酶抑制剂因子的相对表达水平低于大鼠肾上腺髓质,而F1F0 - ATP酶α亚基的情况则相反。目前的结果表明,豚鼠嗜铬细胞对线粒体抑制剂的CA分泌反应比大鼠嗜铬细胞更强,且前者更高的敏感性是由于在ΔΨm去极化条件下F1F0 - ATP酶反向运转程度更大,从而导致ATP减少。