Prüfer K, Jirikowski G F
Department of Anatomy II, University of Jena, Germany.
Biochem Pharmacol. 1996 Feb 9;51(3):247-52. doi: 10.1016/0006-2952(96)02130-2.
1.25-dihydroxyvitamin D3 is of clinical importance (e.g. in the treatment of psoriasis) given its ability to regulate the proliferation and differentiation of human keratinocytes. 1.25-Dihydroxyvitamin D3 mediates its action via genomic and nongenomic pathways. The nongenomic actions begin with the activation of phospholipase C and the subsequent rapid rise in calcium within the cells. We incorporated 1.25-dihydroxyvitamin D3 in liposomes of varying compositions in an attempt to improve their effect/negative side effect ratio. The influence of empty liposomes (1 mM) and free and liposomally incorporated 1.25-dihydroxyvitamin D3 (10 nM) on the rapid release of sulfidoleucotrien and inositole 1,4,5 triphosphate was examined in keratinocytes in vitro. Free 10 nM 1.25-dihydroxyvitamin D3 provoked a rapid rise in sulfidoleucotriens within 30 seconds, followed by a swift decrease in sulfidoleucotrien and inositole 1,4,5-triphosphate concentration after 10 minutes. Empty liposomes and liposomal-incorporated 1.25-dihydroxyvitamin D3 did not show such a strong effect. These results suggest the occurrence of specific binding sites for 1.25-dihydroxyvitamin D3 on the membrane level that are incapable of recognizing 1.25-dihydroxyvitamin D3 trapped within liposomal membrane.
1,25 - 二羟基维生素D3具有临床重要性（如在银屑病治疗中），因为它能够调节人类角质形成细胞的增殖和分化。1,25 - 二羟基维生素D3通过基因组和非基因组途径介导其作用。非基因组作用始于磷脂酶C的激活以及随后细胞内钙的快速升高。我们将1,25 - 二羟基维生素D3掺入不同组成的脂质体中，试图提高其效果/副作用比。在体外角质形成细胞中检测了空脂质体（1 mM）以及游离的和脂质体包裹的1,25 - 二羟基维生素D3（10 nM）对硫代白三烯和肌醇1,4,5 - 三磷酸快速释放的影响。游离的10 nM 1,25 - 二羟基维生素D3在30秒内引发硫代白三烯迅速升高，随后在10分钟后硫代白三烯和肌醇1,4,5 - 三磷酸浓度迅速下降。空脂质体和脂质体包裹的1,25 - 二羟基维生素D3未显示出如此强烈的作用。这些结果表明在膜水平上存在1,25 - 二羟基维生素D3的特异性结合位点，这些位点无法识别被困在脂质体膜内的1,25 - 二羟基维生素D3。
