Andjus R K, Konjević D, Damjanović I, Gacić Z
Center for Multidisciplinary Studies, University of Belgrade, 29 Novembra 142, 11000, Belgrade, Yugoslavia.
Brain Res. 2000 Jun 23;868(2):176-90. doi: 10.1016/s0006-8993(00)02328-3.
In view of the use of synthetic propentofylline (PPF) as a protective agent in brain ischemia, its possible side effects on vision capacities have been explored by electroretinography in comparative experiments with theophylline. We used eyecup preparations of small-spotted dogfish sharks and of European eels, particularly suitable for long-lasting experiments. The drug exerted profound but reversible modifications of ERG records: (1) a dose-dependent increase of the amplitude and duration of the chemically isolated late receptor potential (LRP), (2) a partial unmasking of LRP, (3) a strong potentiation of the LRP-unmasking effect of low temperature, (4) a potentiation of light adaptation effects, and (5) a strong potentiation of the post-illumination hyperexcitability. The effects were explicable as due to a strong phosphodiesterase (PDE) inhibiting, cyclic guanosine monophosphate (cGMP) promoting, action of the drug. The effects were considerably stronger, or even of opposite sign, in comparison to those of the chemically related theophylline. PPF did not seriously affect the ERG c-wave originating in the pigment epithelium. The results suggested that the effects of PPF on vision may not seriously hamper the therapeutic use of the drug. They indicated, on the other hand, that PPF was a retinoactive drug of potential usefulness in the exploration of the complex biochemical events underlying visual transduction.
鉴于合成戊四氮（PPF）在脑缺血中用作保护剂，我们通过视网膜电图，在与茶碱的对比实验中，探究了其对视觉能力可能产生的副作用。我们使用了特别适合进行长期实验的黄斑星鲨和欧洲鳗鲡的眼杯制剂。该药物对视网膜电图记录产生了深刻但可逆的改变：（1）化学分离的晚期受体电位（LRP）的振幅和持续时间呈剂量依赖性增加；（2）LRP部分暴露；（3）低温对LRP的暴露效应有强烈的增强作用；（4）对光适应效应有增强作用；（5）对光照后超兴奋性有强烈的增强作用。这些效应可以解释为该药物具有强烈的磷酸二酯酶（PDE）抑制和环磷酸鸟苷（cGMP）促进作用。与化学结构相关的茶碱相比，这些效应要强得多，甚至方向相反。PPF对起源于色素上皮的视网膜电图c波没有严重影响。结果表明，PPF对视觉的影响可能不会严重妨碍该药物的治疗用途。另一方面，这些结果表明PPF是一种具有潜在用途的视活性药物，可用于探索视觉转导背后复杂的生化事件。
