Kotoyori J, Tokuda H, Oiso Y, Kozawa O
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Cell Signal. 1993 Jul;5(4):411-6. doi: 10.1016/0898-6568(93)90080-6.
We investigated the effects of retinoic acid (RA) on the signalling pathways by prostaglandin E2 (PGE2) in osteoblast-like MC3T3-E1 cells. The pretreatment with RA significantly inhibited the formation of inositol phosphates induced by 10 microM PGE2 in a dose-dependent manner in the range between 0.1 nM and 0.1 microM, without affecting protein contents in the cultured cells. This effect of RA was dependent on the time of pretreatment up to 8 h. However, RA had little effect on the formation of inositol phosphates induced by NaF, a GTP-binding protein activator. On the other hand, RA significantly inhibited PGE2-induced cAMP accumulation in a dose-dependent manner between 0.1 nM and 0.1 microM. This effect of RA was dependent on the time of pretreatment up to 8 h. RA also inhibited the cAMP accumulation induced by NaF or forskolin which directly activates adenylate cyclase. These results strongly suggest that RA modulates the signalling by PGE2 in osteoblast-like cells as follows: the inhibitory effect on the phosphoinositide hydrolysis is exerted at the point between PGE2 receptor and GTP-binding protein, and the inhibitory effect on the cAMP production is exerted at a point downstream from adenylate cyclase.
我们研究了视黄酸（RA）对成骨样MC3T3-E1细胞中前列腺素E2（PGE2）信号通路的影响。在0.1 nM至0.1 microM范围内，RA预处理以剂量依赖性方式显著抑制了10 microM PGE2诱导的肌醇磷酸形成，且不影响培养细胞中的蛋白质含量。RA的这种作用在长达8小时的预处理时间内具有依赖性。然而，RA对由GTP结合蛋白激活剂氟化钠诱导的肌醇磷酸形成几乎没有影响。另一方面，RA在0.1 nM至0.1 microM之间以剂量依赖性方式显著抑制了PGE2诱导的cAMP积累。RA的这种作用在长达8小时的预处理时间内具有依赖性。RA还抑制了由氟化钠或直接激活腺苷酸环化酶的福斯可林诱导的cAMP积累。这些结果强烈表明，RA如下调节成骨样细胞中PGE2的信号传导：对磷酸肌醇水解的抑制作用在PGE2受体和GTP结合蛋白之间的点发挥，对cAMP产生的抑制作用在腺苷酸环化酶下游的点发挥。
