Furuichi T, Kawata S, Asoh Y, Kumaki K, Ohyama Y
Fuji-Gotemba Research Laboratory, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Life Sci. 1998;62(5):453-9. doi: 10.1016/s0024-3205(97)01139-9.
In order to investigate the in vivo mechanisms of target gene activation by vitamin D3 analogs, we compared the effects of two vitamin D3 analogs, 22-oxa-1alpha,25-(OH)2D3 (OCT) and 2beta (3-hydroxypropoxy) -1alpha,25-(OH)2D3 (ED-71) with that of 1alpha,25-(OH)2D3 on 1alpha,25-(OH)2D3 -24-hydroxylase[24(OH)ase] mRNA expression in the kidney and intestine of normal rats. In these experiments, all three compounds induced 24(OH)ase mRNA, but the time course of induction for each respective treatment was clearly different. OCT caused the most rapid onset of increased 24(OH)ase mRNA expression and its subsequent return to pre-injection levels. In marked contrast, ED-71 was the slowest to increase expression which was prolonged over that observed with the other compounds tested. These differences probably relate to the pharmacokinetic properties of these analogs, which are mainly generated by the affinity of analogs for the vitamin D-binding protein(DBP).
为了研究维生素D3类似物激活靶基因的体内机制，我们比较了两种维生素D3类似物，即22-氧杂-1α,25-二羟基维生素D3（OCT）和2β-(3-羟基丙氧基)-1α,25-二羟基维生素D3（ED-71）与1α,25-二羟基维生素D3对正常大鼠肾脏和肠道中1α,25-二羟基维生素D3-24-羟化酶[24(OH)ase]mRNA表达的影响。在这些实验中，所有三种化合物均诱导了24(OH)ase mRNA的表达，但每种处理的诱导时间进程明显不同。OCT引起24(OH)ase mRNA表达增加的起效最快，随后又恢复到注射前水平。与之形成鲜明对比的是，ED-71增加表达的速度最慢，且其持续时间比其他受试化合物更长。这些差异可能与这些类似物的药代动力学特性有关，而这些特性主要由类似物对维生素D结合蛋白（DBP）的亲和力产生。
