Permeability transition pore closure promoted by quinine.
The mitochondrial membrane permeability transition induced by Ca2+ is inhibited by quinine in a dose-dependent fashion. Competition experiments strongly suggest that quinine displaces Ca2+ bound to the inner membrane. This is supported by experiments showing that quinine inhibits Ca2+-dependent but not Ca2+-independent mitochondrial swelling induced by phenylarsine oxide. As with Ca2+ chelators, quinine induces permeability transition pore closure preventing the contraction induced by poly(ethylene glycol) 2000 in mitochondria preswollen by incubation in KSCN medium containing Ca2+ and inorganic phosphate. These results suggest that quinine dislodges Ca2+ bound to the protein site, which triggers pore opening.
Catisti
R
R
Departamento de Patologia Clinica, NMCE, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brasil.
Vercesi
A E
AE
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010539:Permeability; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D013861:Thiocyanates / Q000494:pharmacology
D009861:Onium Compounds; D009943:Organophosphorus Compounds; D013861:Thiocyanates; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000001:Calcimycin; D000968:Antimycin A; D011803:Quinine; D002118:Calcium; C009941:potassium thiocyanate; C013289:tetraphenylphosphonium