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Importance of sulfhydryl groups for the uncoupling activity of non steroidal acidic anti inflammatory drugs and valinomycin in oxidative phosphorylation

par Famaey, Jean Pierre ;Mockel, Jean
Référence Biochemical pharmacology, 22, 12, page (1487-1498)
Publication Publié, 1973

Article révisé par les pairs

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Résumé :

In media at pH 7.4 the uncoupling activity on oxidative phosphorylation with sodium succinate (5 mM) as substrate was studied in liver mitochondria for many antiinflammatory drugs (e.g., ibuprofen, 0.25 mM; flufenamic acid, 0.20 mM; pyrazinobutazone, 0.25 mM; indomethacin, 0.20 mM; and methiazinic acid, 1 mM). Mersalyl (0.035 mM) does not inhibit the respiration induced by 2,4 dinitrophenol, but inhibits respiration induced by all these drugs. This inhibition was not reversed by 2,4 dinitrophenol (20 μM), Janus Green B (50 μM) or any other uncoupling agents in media with or without phosphate. This proved that this action is independent of the ability of Mersalyl to prevent phosphate penetration into mitochondria. Meanwhile, cysteine (0.15 mM) was able to reverse the inhibition of Mersalyl in media with as well as without phosphate and restored the uncoupling activity of the anti inflammatory drugs. This competition between cysteine and Mersalyl is 'dose dependent'. A similar action of Mersalyl and cysteine was also observed on the uncoupling activity of valinomycin (0.2 μg). The results suggest that acidic anti inflammatory drugs and valinomycin exert their uncoupling activity by way of fixation on membrane sites rich in sulfhydryl groups. The sites might be similar for the two kinds of drugs. There is a slight inhibition of the uncoupling activity of valinomycin and acidic anti inflammatory drugs observed with nupercaine (0.6 mM).