Effect of local anesthetic ropivacaine on the energy metabolism of Ehrlich ascites tumor cells.
The effect of local anesthetic ropivacaine on the energy metabolism of Ehrlich ascites tumor cells has been investigated. Ropivacaine impaired energy metabolism of Ehrlich ascites tumor cells by affecting primarily mitochondrial metabolism. Even at low concentrations ropivacaine decreased the rate of oxygen uptake, but its effect was remarkably higher on the uncoupled respiration and, in both cases, it was strongly enhanced by hydrophobic anion tetraphenylboron (TPB-). The decrease of oxygen uptake was ascribed to an impairment of electron transport from site 1- and 2-entering substrates to respiratory chain. The inhibition of respiration, coupled to a true uncoupling mechanism by an electrophoretic mechanism, impaired ADP phosphorylation, decreased ATP content, and collapsed mitochondrial membrane potential. Ropivacaine, at all concentrations tested, stimulated aerobic lactate production, and this increase, in addition to the inhibition of respiration, was also due to an activation of mitochondrial ATPase.
Di Padova
M
M
Laboratory of Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Barbieri
R
R
Fanciulli
M
M
Arcuri
E
E
Floridi
A
A
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D000077212:Ropivacaine; D013997:Time Factors
D000577:Amides; D000779:Anesthetics, Local; D019344:Lactic Acid; D000077212:Ropivacaine; D000255:Adenosine Triphosphate