Effect of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195), a specific ligand of the peripheral benzodiazepine receptor, on the lipid fluidity of mitochondria in human glioma cells.

When human glioma cells were incubated for 24 hr in serum-free medium with nanomolar concentrations of 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide (PK11195), a specific ligand of the peripheral benzodiazepine receptor (PBR), a significant increase in the membrane fluidity of mitochondria isolated from these cells was registered. These effects were not observed with a shorter incubation time (2 hr) of the cells with PK11195 nor in the presence of serum. Other significant associated changes were observed: a significant increase of 16+/-4% of [3H]thymidine incorporation into DNA was detected in cells in the presence of PK11195 in serum-free medium, and an increase of 33+/-5% as compared to controls in nonyl acridine orange uptake, as indicator of mitochondrial mass, was also registered in cells treated with 10 nM PK11195. [3H]PK11195 binding was decreased in cells incubated with PK11195; a 45% decrease compared to controls was obtained. In view of the effect of PBR ligands on DNA synthesis, changes in mitochondrial lipid metabolism through interaction with PBRs might lead to biogenesis of mitochondria to support the increased metabolic requirements for cell division, which is even higher in malignant cells.