Ionophoretic-like properties of ketorolac for calcium.
Ketorolac is an analgesic drug known to induce its therapeutic effect by inhibiting prostaglandin synthesis. In this work we introduce the nonsteroidal antialgesic drug as a compound with ionophoretic properties for calcium ions, showing that ketorolac induces mitochondrial Ca++ release. This reaction did not depend on an uncoupler-like action, because the drug does not collapse the internal negative membrane potential nor does it affect oxidative phosphorylation. In addition, it is shown that ketorolac ferries calcium ions into energized liposomes and has a hydrophobic phase with an affinity constant of 4 x 10(-3). The therapeutic action of ketorolac is related to its ionophoretic properties in addition to its well known inhibitory effect on the cyclooxygenase enzyme.
Chàvez
R
R
Departamento de Bioquìmica, Instituto Nacional de Cardiologìa, Ignacio Chàvez, Mexico, D.F., Mexico.
Bravo
C
C
Zazueta
C
C
Pichardo
J
J
Uribe
A
A
Corona
N
N
Reyes-Vivas
H
H
González
C
C
Chàvez
E
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology*; D020910:Ketorolac; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D012680:Sensitivity and Specificity; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007476:Ionophores; D008051:Lipid Bilayers; D008081:Liposomes; D012430:Ruthenium Red; D014046:Tolmetin; D002118:Calcium; D020910:Ketorolac