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Effects of the local anesthetic bupivacaine on mitochondrial energy metabolism: change from uncoupling to decoupling depending on the respiration state
Author(s) -
Sztark François,
Ouhabi Rachid,
Dabadie Philippe,
Mazat JeanPierre
Publication year - 1997
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549700204811
Subject(s) - bupivacaine , respiration , oxidative phosphorylation , uncoupling agents , mitochondrion , cellular respiration , respiratory chain , local anesthetic , electron transport chain , chemistry , biology , biophysics , biochemistry , pharmacology , anatomy , neuroscience
Abstract 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