Ito S, Sugama K, Inagaki N, Fukui H, Giles H, Wada H, Hayaishi O
Department of Cell Biology, Osaka Bioscience Institute, Japan.
Glia. 1992;6(1):67-74. doi: 10.1002/glia.440060109.
Accumulating evidence has revealed that astrocytes are potential targets for various neurotransmitters. Here we investigated the effects of prostaglandins (PGs) on signal transduction in purified primary cultures of rat type-1 and type-2 astrocytes. PGF2 alpha, PGD2, and 9 alpha,11 beta-PGF2, a metabolite of PGD2 and a stereoisomer of PGF2 alpha, evoked a rapid rise in the intracellular Ca2+ concentration ([Ca2+]i) in type-1, but not in type-2, astrocytes. STA2, a stable analogue of thromboxane A2, was less effective, and PGE2 showed little effect. The PG-induced rise in [Ca2+]i was not blocked by an antagonist of either PGD2 receptor or thromboxane A2 receptor. PGF2 alpha and 9 alpha,11 beta-PGF2 stimulated rapid formation of inositol trisphosphate followed by inositol bisphosphate and inositol monophosphate. On the other hand, PGE2 increased the intracellular level of cyclic AMP in type-2 astrocytes, rather than in type-1 astrocytes. The potency of PGs for cyclic AMP formation was in the following order: PGE2 greater than PGE1 greater than or equal to STA2 much greater than iloprost, a stable analogue of PGI2. PGD2 and PGF2 alpha had no effect on cyclic AMP formation. These results demonstrate that type-1 astrocytes preferentially express PGF2 alpha receptors, the activation of which leads to phosphoinositide metabolism and [Ca2+]i elevation, whereas type-2 astrocytes possess PGE receptors that are linked to cyclic AMP formation.
越来越多的证据表明，星形胶质细胞是各种神经递质的潜在靶点。在此，我们研究了前列腺素（PGs）对纯化的原代大鼠1型和2型星形胶质细胞信号转导的影响。前列腺素F2α（PGF2α）、前列腺素D2（PGD2）以及PGD2的代谢产物和PGF2α的立体异构体9α,11β - PGF2，可使1型星形胶质细胞而非2型星形胶质细胞的细胞内钙离子浓度（[Ca2+]i）迅速升高。血栓素A2的稳定类似物STA2作用较弱，而前列腺素E2（PGE2）几乎没有作用。PG诱导的[Ca2+]i升高不受PGD2受体或血栓素A2受体拮抗剂的阻断。PGF2α和9α,11β - PGF2刺激肌醇三磷酸快速形成，随后是肌醇二磷酸和肌醇单磷酸。另一方面，PGE2增加2型星形胶质细胞而非1型星形胶质细胞内的环磷酸腺苷（cAMP）水平。PGs对cAMP形成的效力顺序如下：PGE2大于前列腺素E1（PGE1）大于或等于STA2远大于前列环素（PGI2）的稳定类似物伊洛前列素。PGD2和PGF2α对cAMP形成没有影响。这些结果表明，1型星形胶质细胞优先表达PGF2α受体，其激活导致磷酸肌醇代谢和[Ca2+]i升高，而2型星形胶质细胞具有与cAMP形成相关的PGE受体。
