Cell surface expression of heat shock proteins in dog neutrophils induced by mitochondrial benzodiazepine receptor ligands.
The effect of peripheral-type benzodiazepines on dog neutrophil stimulation was studied. Ro 5-4864 (a specific ligand of mitochondrial benzodiazepine receptor) and diazepam (which binds both to mitochondrial and central benzodiazepine receptors) did not show any direct toxic effect against neutrophils. PK 11195, a putative antagonist of the mitochondrial benzodiazepine receptor and an isoquinoline derivative, had a direct toxic effect at a concentration of 5 x 10(-5) M (72% of cells were viable). Ro 5-4864 (10(-6)-10(-4) M) and diazepam (10(-6)-2.5 x 10(-4) M) induced an intracellular oxidative stress in dog neutrophils. These compounds, in a micromolar range, also induced a concentration-dependent cell surface expression of heat shock protein (HSP) families. The percentages of positive cells that express these proteins were: 76.2% for HSP 27 kDa; 54.3% for HSP 72 kDa and 69.6% for HSP 90 kDa for Ro 5-4864 (10(-4) M), and 66.7% for HSP 27 kDa; 45.4% for HSP 72 kDa and 78.3 for HSP 90 kDa for diazepam (2.5 x 10(-4) M). It appears that this HSP expression, induced by peripheral-type benzodiazepines could be mediated by an intracellular oxidative stress.
Camins
A
A
Laboratory of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Barcelona, Spain.
Diez-Fernandez
C
C
Camarasa
J
J
Escubedo
E
E
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004285:Dogs; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D001570:Benzodiazepinones; D006360:Heat-Shock Proteins; D007546:Isoquinolines; D008024:Ligands; D017382:Reactive Oxygen Species; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D003975:Diazepam; C037850:PK 11195