Effects of decoquinate and clopidol on electron transport in mitochondria of Eimeria tenella (Apicomplexa: Coccidia).
Resistance of the chicken coccidium Eimeria tenella to the anticoccidial agents decoquinate and clopidol, and the synergistic activity of mixtures of these compounds have been confirmed in vivo. Inhibition of electron transport by decoquinate and clopidol has been studied in mitochondria isolated from unsporulated oocysts of the same lines of E. tenella as those used in the in vivo studies. Electron transport in mitochondria of a drug sensitive line was susceptible to inhibition by both decoquinate and clopidol, and mitochondria isolated from lines made resistant to one or the other of these compounds showed a corresponding resistance at the level of electron transport. Combinations of low concentrations of decoquinate and clopidol caused a greater inhibition of electron transport than expected from summation of their individual actions. Isobolograms showed that decoquinate and clopidol in fact potentiated each other's effect on electron transport. Induced resistance to either decoquinate or clopidol resulted in an increased sensitivity of electron transport to inhibition by the other drug. Cytochrome spectra of E. tenella mitochondria and a biphasic response of NADH-oxidase and terminal oxidase activity to inhibition by cyanide or azide suggest the presence of two functional terminal oxidases. There is a correlation between the resistance of electron transport to inhibition by decoquinate or clopidol and the susceptibility to inhibition by cyanide or azide. Mitochondrial electron transport that is more resistant to inhibition by decoquinate exhibits greater sensitivity to cyanide and azide; electron transport that is more resistant to inhibition by clopidol exhibits a decreased sensitivity to cyanide and azide. Resistance to decoquinate and clopidol is discussed in view of a possibly branched electron transport chain in mitochondria of E. tenella.
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002645:Chickens; D003007:Clopidol / Q000494:pharmacology*; D003048:Coccidiosis / Q000188:drug therapy; D003486:Cyanides / Q000494:pharmacology; D003580:Cytochromes / Q000378:metabolism; D003667:Decoquinate / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D004539:Eimeria / Q000187:drug effects* / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D006912:Hydroxyquinolines / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*
D001386:Azides; D003486:Cyanides; D003580:Cytochromes; D006912:Hydroxyquinolines; D011725:Pyridines; D003667:Decoquinate; D003007:Clopidol; D010088:Oxidoreductases