Takahashi H, Tamura T, Iizuka H
Department of Dermatology, Asahikawa Medical College, Japan.
J Dermatol Sci. 1996 Feb;11(2):121-8. doi: 10.1016/0923-1811(95)00428-9.
Using fetal rat keratinizing epidermal cells (FRSK), the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on adenylate cyclase system were investigated. The beta-adrenergic adenylate cyclase response was significantly increased by the stimulation of 1 x 10(-7) M 1,25(OH)2D3. The effect was observed by 6 h and continued for at least 48 h. The 1,25(OH)2D3-induced beta-adrenergic augmentation effect was dose-dependent and the maximal response was observed at a concentration of 1 x 10(-7) M 1,25(OH)2D3. Other adenylate cyclase systems (adenosine, prostaglandin E2 and histamine) were not affected by treatment with 1,25(OH)2D3. The thymidine incorporation in FRSK cells was not significantly affected by 1,25(OH)2D3 treatment. Forskolin-induced cyclic AMP accumulation was significantly increased by 1,25(OH)2D3 treatment. Cholera toxin-induced cyclic AMP accumulation was moderately increased, but this was statistically not significant. Northern blot hybridization showed that none of the mRNAs (the beta 2-adrenergic receptor, the alpha subunits of the stimulatory or inhibitory guanine nucleotide binding proteins, Gs alpha, Gi2 alpha, Gi3 alpha) were significantly altered by 1,25(OH)2D3 treatment. We have already reported that the beta-adrenergic response was increased by dexamethasone and inhibited by retinoids in FRSK cells. The addition of both 1,25(OH)2D3 and dexamethasone to the incubation medium resulted in an additive augmentation. On the other hand, the beta-adrenergic augmentation by the 1,25(OH)2D3 treatment was suppressed by the addition of all trans-retinoic acids. Our results indicate that 1,25(OH)2D3 induces beta-adrenergic augmentation without an alternation of thymidine incorporation of FRSK cells.
利用胎鼠角质形成表皮细胞（FRSK），研究了1,25 - 二羟基维生素D3（1,25(OH)2D3）对腺苷酸环化酶系统的影响。1×10^(-7) M的1,25(OH)2D3刺激可显著增强β - 肾上腺素能腺苷酸环化酶反应。6小时时可观察到该效应，并持续至少48小时。1,25(OH)2D3诱导的β - 肾上腺素能增强效应呈剂量依赖性，在1×10^(-7) M 1,25(OH)2D3浓度下观察到最大反应。其他腺苷酸环化酶系统（腺苷、前列腺素E2和组胺）不受1,25(OH)2D3处理的影响。1,25(OH)2D3处理对FRSK细胞中的胸苷掺入没有显著影响。1,25(OH)2D3处理可显著增加福斯高林诱导的环磷酸腺苷（cAMP）积累。霍乱毒素诱导的cAMP积累有适度增加，但在统计学上不显著。Northern印迹杂交显示，1,25(OH)2D3处理后，没有一种mRNA（β2 - 肾上腺素能受体、刺激性或抑制性鸟嘌呤核苷酸结合蛋白的α亚基，Gsα、Gi2α、Gi3α）发生显著改变。我们已经报道，在FRSK细胞中，地塞米松可增强β - 肾上腺素能反应，而视黄酸则抑制该反应。在孵育培养基中同时添加1,25(OH)2D3和地塞米松会产生相加性增强作用。另一方面，添加全反式维甲酸可抑制1,25(OH)2D3处理引起的β - 肾上腺素能增强。我们的结果表明，1,25(OH)2D3可诱导β - 肾上腺素能增强，而不改变FRSK细胞的胸苷掺入。
