Camins A, Diez-Fernandez C, Camarasa J, Escubedo E
Laboratory of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Barcelona, Spain.
Immunopharmacology. 1995 Mar;29(2):159-66. doi: 10.1016/0162-3109(94)00055-k.
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.
研究了外周型苯二氮䓬类药物对犬中性粒细胞刺激的影响。Ro 5-4864（线粒体苯二氮䓬受体的特异性配体）和地西泮（同时结合线粒体和中枢苯二氮䓬受体）对中性粒细胞未显示出任何直接毒性作用。PK 11195是一种推测的线粒体苯二氮䓬受体拮抗剂，为异喹啉衍生物，在浓度为5×10⁻⁵ M时具有直接毒性作用（72%的细胞存活）。Ro 5-4864（10⁻⁶ - 10⁻⁴ M）和地西泮（10⁻⁶ - 2.5×10⁻⁴ M）在犬中性粒细胞中诱导细胞内氧化应激。这些化合物在微摩尔范围内还诱导热休克蛋白（HSP）家族的浓度依赖性细胞表面表达。表达这些蛋白的阳性细胞百分比为：Ro 5-4864（10⁻⁴ M）时，27 kDa的HSP为76.2%；72 kDa的HSP为54.3%；90 kDa的HSP为69.6%；地西泮（2.5×10⁻⁴ M）时，27 kDa的HSP为66.7%；72 kDa的HSP为45.4%；90 kDa的HSP为78.3%。外周型苯二氮䓬类药物诱导的这种HSP表达似乎可能由细胞内氧化应激介导。
