Bouillon R, Allewaert K, Xiang D Z, Tan B K, van Baelen H
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Belgium.
J Bone Miner Res. 1991 Oct;6(10):1051-7. doi: 10.1002/jbmr.5650061006.
The affinity of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] and analogs with side-chain modifications [MC 903 or calcipotriol, MC 1147 or 24,24-dihomo-1 alpha,25-(OH)2D3 and 1,25-(OH)2-16ene-23yne-D3] for the vitamin D receptor and the serum vitamin D binding protein (DBP) were compared. The affinity of MC 903 for the receptor from chick and rat duodenum or from human peripheral blood mononuclear cells or HL-60 cells varied between 60 and 100% relative to the affinity of 1,25-(OH)2D3. The relative affinity of 1,25-(OH)2-16ene-23yne-D3 and MC 1147 varied for the same receptors between 45-70 and 3.5-25%, respectively. The relative affinity of MC 903 for human DBP was 30-fold decreased, whereas the two other analogs did not bind to DBP at all even in more than 1000-fold excess. The in vitro biologic activity of 1 alpha,25-(OH)2D3 on phytohemagglutinin-stimulated normal human lymphocyte proliferation was markedly inhibited by the addition of physiologic amounts of DBP to the cell culture medium. No such inhibition was observed when MC 903 or 1147 was evaluated similarly. DBP therefore reversed the rank order of the in vitro potency of these analogs. Intramuscular injections for 10 consecutive days to vitamin D-deficient chicks demonstrated a greater than or equal to 100-fold lower biologic activity of MC 903, MC 1147, and 1,25-(OH)2-16ene-23yne-D3 compared to that of 1 alpha,25-(OH)2D3 as evaluated by serum calcium and osteocalcin concentrations, as well as by duodenal calbindin D28K and bone calcium content.(ABSTRACT TRUNCATED AT 250 WORDS)
比较了1α,25 - 二羟基维生素D3 [1α,25-(OH)2D3] 及其具有侧链修饰的类似物 [MC 903或骨化三醇、MC 1147或24,24 - 双高 - 1α,25-(OH)2D3以及1,25-(OH)2 - 16 - 烯 - 23 - 炔 - D3] 对维生素D受体和血清维生素D结合蛋白 (DBP) 的亲和力。MC 903对鸡和大鼠十二指肠、人外周血单个核细胞或HL - 60细胞受体的亲和力相对于1,25-(OH)2D3的亲和力在60%至100%之间变化。1,25-(OH)2 - 16 - 烯 - 23 - 炔 - D3和MC 1147对相同受体的相对亲和力分别在45% - 70%和3.5% - 25%之间变化。MC 903对人DBP的相对亲和力降低了30倍，而另外两种类似物即使在超过1000倍过量的情况下也根本不与DBP结合。向细胞培养基中添加生理量的DBP可显著抑制1α,25-(OH)2D3对植物血凝素刺激的正常人淋巴细胞增殖的体外生物学活性。对MC 903或1147进行类似评估时未观察到这种抑制作用。因此，DBP颠倒了这些类似物体外效力的等级顺序。连续10天对维生素D缺乏的雏鸡进行肌肉注射，结果显示，与1α,25-(OH)2D3相比，通过血清钙和骨钙素浓度以及十二指肠钙结合蛋白D28K和骨钙含量评估，MC 903、MC 1147和1,25-(OH)2 - 16 - 烯 - 23 - 炔 - D3的生物学活性降低了100倍以上。(摘要截断于250字)
