Diazoxide and pinacidil uncouple pyruvate-malate-induced mitochondrial respiration.
We investigated the effects of K(ATP) channel openers diazoxide and pinacidil on the respiration rate and membrane potential (deltapsi) of rat heart mitochondria, oxidizing pyruvate and malate. Diazoxide and pinacidil (58.8-1348.3 microM) increased the V2 (-ADP) respiration rate accordingly by 13-208% and 30-273% and decreased the deltapsi by 2-17% and 6-55%. These effects were also similar in the respiration medium without K+. Moreover, carboxyatractyloside completely abolished diazoxide- and pinacidil-induced uncoupling, indicating a role for the mitochondrial adenine nucleotide translocase in this process.
Kopustinskiene
Dalia M
DM
Institute for Biomedical Research, Kaunas University of Medicine, Lithuania. bioch@kmu.lt
Jovaisiene
Jovita
J
Liobikas
Julius
J
Toleikis
Adolfas
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects*; D020110:Pinacidil / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014475:Uncoupling Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D008293:Malates; D014475:Uncoupling Agents; D020110:Pinacidil; C030298:malic acid; D019289:Pyruvic Acid; D000226:Mitochondrial ADP, ATP Translocases; D003981:Diazoxide