Chloroquine-sensitive transplasmalemma electron transport in Tetrahymena pyriformis: a hypothesis for control of parasite protozoa through transmembrane redox.
Plasma membrane electron transport was studied in a protozoan cell, Tetrahymena pyriformis, by assaying transmembrane ferricyanide reduction and the reduction of iron compounds. The rates of ferricyanide reduction varied between 0.5 and 2.5 mumol/g dry wt. per min, with a pH optimum at 7.0-7.5. Other active non-permeable electron acceptors, with redox potentials from +360 to -125 mV, were cytochrome c, hexaammine ruthenium chloride, ferric-EDTA, ammonium ferric citrate, and indigo di-, tri- and tetrasulfonates. It was found that Tetrahymena cells can reduce external electron acceptors with redox potentials at pH 7.0 down to -125 mV. Ferricyanide stimulates ciliary action. Transmembrane ferricyanide reduction by Tetrahymena was not inhibited by such mitochondrial inhibitors as antimycin A, 2-n-heptyl-4-hydroxyquinoline N-oxide, or potassium cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Tetrahymena appears to involve a plasma membrane electron transport chain similar to those of other animal cells. As in other cells, the transmembrane electron transport is associated with proton release which may be involved in internal pH control. The transmembrane redox system differs from that of mammalian cells in a 20-fold greater sensitivity to chloroquine and quinacrine. The Tetrahymena ferricyanide reduction is also inhibited by chlorpromazine and suramin. Sensitivity to these drugs indicates that the transplasma membrane electron transport and associated proton pumping may be a target for drugs used against malaria, Trypanosomes and other protozoa.
Barr
R
R
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
Branstetter
B A
BA
Rajnicek
A
A
Crane
F L
FL
Löw
H
H
D000818:Animals; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D005292:Ferricyanides / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D013769:Tetrahymena pyriformis / Q000378:metabolism*
D005292:Ferricyanides; C007931:hexacyanoferrate III; D002738:Chloroquine; D011796:Quinacrine; D010100:Oxygen