Leukotriene C4 inhibits ATP-dependent transport of glutathione S-conjugate across rat heart sarcolemma. Implication for leukotriene C4 translocation mediated by glutathione S-conjugate carrier.
Sarcolemmal vesicles prepared from rat heart exhibited ATP-dependent uptake of S-(2,4-dinitrophenyl)glutathione (DNP-SG), which obeyed Michaelis-Menten kinetics with an apparent Km of 21 microM for DNP-SG and a Vmax of 0.27 nmol.10 min-1.mg protein-1. Several model glutathione S-conjugates inhibited DNP-SG uptake, but leukotriene C4 inhibited uptake much more significantly even at lower concentrations (competitive inhibition, Ki = 1.5 microM). However, leukotrienes D4 and E4, which lack the gamma-glutamyl moiety, were less effective. The results suggest that the ATP-dependent transport system has a high affinity for leukotriene C4, and may be responsible for the translocation of this compound.
Ishikawa
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Department of Biochemistry, Osaka University Medical School, Japan.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D013189:SRS-A / Q000494:pharmacology*; D012508:Sarcolemma / Q000378:metabolism*
D013189:SRS-A; C030190:S-(2,4-dinitrophenyl)glutathione; D000255:Adenosine Triphosphate; D005978:Glutathione