Effects of the local anesthetic bupivacaine on mitochondrial energy metabolism: change from uncoupling to decoupling depending on the respiration state.
The local anesthetic bupivacaine has been found to uncouple oxidative phosphorylation. However, the precise mechanisms of bupivacaine uncoupling have not been elucidated. In the present paper, we demonstrate that the uncoupling effect of the local anesthetic depends on the respiration state. In state 4-respiration (no ADP phosphorylation), bupivacaine acts as a true protonophoretic uncoupler. On the other hand, in state 3-respiration (ADP phosphorylation), bupivacaine induces a change in proton pump stoichiometry and appears to be a decoupler (slip inducer). Moreover, at high concentration, the local anesthetic inhibits the respiratory chain itself. Thus, the divergent reports in the literature on the action of bupivacaine show in fact the various mechanisms by which the local anesthetic may alter mitochondrial energy metabolism.
Sztark
F
F
Laboratoire d'Anesthésiologie (GRAF), Université Victor Segalen Bordeaux 2, France. sztark@hippocrate.u-bordeaux2.fr
Ouhabi
R
R
Dabadie
P
P
Mazat
J P
JP
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014475:Uncoupling Agents / Q000494:pharmacology
D000779:Anesthetics, Local; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002045:Bupivacaine