title: Inactivation of mitochondrial permeability transition pore by octylguanidine and octylamine.
abstract: Mitochondrial permeability transition occurs through a Ca2+-dependent opening of a transmembrane pore, whose identity has been attributed to that of the adenine nucleotide translocase (ANT). In this work, we induced permeability transition by adding 0.5 microM carboxyatractyloside. The process was evaluated analyzing Ca2+ efflux, a drop in transmembrane electric gradient, and swelling. We found that the amphiphyllic cations octylguanidine and octylamine, at the concentration of 100 microM, inhibited, almost completely, nonspecific membrane permeability. Hexylguanidine, hexylamine, as well as guanidine chloride and hydroxylamine failed to do so. The inhibition was reversed after the addition of 40 mM Li+, Na+ K+, Rb+, or Cs+; K+ was the most effective. We propose that the positive charge of the amines interact with negative charges of membrane proteins, more likely the ADP/ATP carrier, while the alkyl chain penetrates into the hydrophobic milieu of the inner membrane, fixing the reagent.
authors.affiliation: Departamento de Bioquímica Instituto Nacional de Cardiología, Ignacio Chávez, UNAM, Mexico, DF, Mexico. echavez@cenids.ssa.gob.mx
authors.forename: E
authors.initials: E
authors.lastname: Chávez
authors.forename: A
authors.initials: A
authors.lastname: Peña
authors.forename: C
authors.initials: C
authors.lastname: Zazueta
authors.forename: J
authors.initials: J
authors.lastname: Ramírez
authors.forename: N
authors.initials: N
authors.lastname: García
authors.forename: R
authors.initials: R
authors.lastname: Carrillo
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011188:Potassium / Q000378:metabolism
chemical_list: D000588:Amines; D006146:Guanidines; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D001278:Atractyloside; C015403:octylguanidine; D000244:Adenosine Diphosphate; C007940:hexylamine; D011188:Potassium; C008699:octylamine; C003853:carboxyatractyloside; D002118:Calcium