Kitanaka J, Ishibashi T, Baba A
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Suita, Japan.
J Neurochem. 1993 Feb;60(2):704-8. doi: 10.1111/j.1471-4159.1993.tb03204.x.
The effect of phloretin on prostaglandin (PG) F2 alpha-induced phosphoinositide hydrolysis and elevation of intracellular Ca2+ concentration was examined in cultured rat astrocytes. Phloretin inhibited PGF2 alpha (1 microM)-induced phosphoinositide hydrolysis in a concentration-dependent manner with an IC50 value of 16 microM. The inhibitory action of phloretin was specific for PGs. The addition of increasing concentrations of phloretin caused progressive shifts of the dose-response curves of PGF2 alpha to the right. In digitonin-permeabilized astrocytes, phloretin (100 microM) inhibited the stimulation induced by PGF2 alpha (1 microM) plus GTP gamma S (50 microM) without affecting that induced by GTP gamma S alone. PGF2 alpha at 1 microM transiently increased astrocytic intracellular Ca2+ concentration in 39% of the cells tested. The response was completely blocked by 100 microM phloretin and the calcium response recovered again after washing out phloretin. These results suggest that phloretin is an antagonist of PGF2 alpha receptor linked to phospholipase C in astrocytes.
在培养的大鼠星形胶质细胞中检测了根皮素对前列腺素（PG）F2α诱导的磷酸肌醇水解和细胞内Ca2+浓度升高的影响。根皮素以浓度依赖的方式抑制PGF2α（1微摩尔）诱导的磷酸肌醇水解，IC50值为16微摩尔。根皮素的抑制作用对前列腺素具有特异性。添加浓度不断增加的根皮素会使PGF2α的剂量反应曲线逐渐向右移动。在洋地黄皂苷通透的星形胶质细胞中，根皮素（100微摩尔）抑制PGF2α（1微摩尔）加GTPγS（50微摩尔）诱导的刺激，而不影响单独由GTPγS诱导的刺激。1微摩尔的PGF2α可使39%受试细胞的星形胶质细胞内Ca2+浓度短暂升高。该反应被100微摩尔根皮素完全阻断，洗去根皮素后钙反应再次恢复。这些结果表明，根皮素是星形胶质细胞中与磷脂酶C相关的PGF2α受体的拮抗剂。
