Londowski J M, Kost S B, Meier W, Labler L, Kumar R
J Pharmacol Exp Ther. 1986 Jun;237(3):837-40.
We have shown previously that the 3-beta-D-glucopyranosides of vitamin D3, 1 alpha-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 are biologically active in vivo. In order to determine whether the presence of the beta-D-glucopyranoside moiety linked to either the C-3, the C-25 or the C-1 hydroxyl function of the molecule affected the biological activity of the conjugates 1, 2, or 3 derived from 1,25-dihydroxyvitamin D3, we administered increasing amounts of compounds to vitamin D-deficient rats maintained on a low calcium diet. The aglycone, 1,25-dihydroxyvitamin D3 (4), also was administered to another group of such animals. When administered i.v., all three beta-D-glucopyranosides increased intestinal calcium transport in doses as low as 50 pmol/rat. A dose of approximately 500 pmol/rat was required to increase bone calcium mobilization in these same animals. The three glucosides were found to be equally active in both biological responses. A dose of only 5 pmol of 1,25-dihydroxyvitamin D3 (4) increased both intestinal calcium transport and bone calcium mobilization. We also performed similar experiments after the p.o. administration of these compounds to vitamin D-deficient rats maintained on a low calcium diet. The glucopyranosides 1, 2 and 3 were able to increase calcium transport in the intestine, as well as mobilize bone calcium at doses of between 500 and 5000 pmol/rat. Once again, the compounds were equipotent, but were less active than 1,25-dihydroxyvitamin D3 (4). After the i.v. or p.o. doses of the glucosides, plasma concentrations of 1,25-dihydroxyvitamin D3 increased in a dose-dependent manner. We conclude that: The C-3, C-25 and C-1 beta-D-glucopyranosides of 1,25-dihydroxyvitamin D3 are biologically active and equipotent in vivo, most likely as a result of hydrolysis to the free aglycone and they are less active than the aglycone in this respect.
我们之前已经表明，维生素D3、1α-羟基维生素D3、1,25-二羟基维生素D3和25-羟基维生素D3的3-β-D-吡喃葡萄糖苷在体内具有生物活性。为了确定与分子的C-3、C-25或C-1羟基功能相连的β-D-吡喃葡萄糖苷部分的存在是否会影响源自1,25-二羟基维生素D3的缀合物1、2或3的生物活性，我们给维持低钙饮食的维生素D缺乏大鼠施用了越来越多的化合物。糖苷配基1,25-二羟基维生素D3（4）也被施用于另一组此类动物。静脉注射时，所有三种β-D-吡喃葡萄糖苷在低至50 pmol/大鼠的剂量下都会增加肠道钙转运。在这些相同的动物中，需要约500 pmol/大鼠的剂量来增加骨钙动员。发现这三种葡糖苷在两种生物学反应中具有同等活性。仅5 pmol的1,25-二羟基维生素D3（4）的剂量就增加了肠道钙转运和骨钙动员。我们还在给维持低钙饮食的维生素D缺乏大鼠口服这些化合物后进行了类似的实验。吡喃葡萄糖苷1、2和3能够在500至5000 pmol/大鼠的剂量下增加肠道钙转运以及动员骨钙。这些化合物再次具有同等效力，但活性低于1,25-二羟基维生素D3（4）。静脉注射或口服葡糖苷剂量后，1,25-二羟基维生素D3的血浆浓度呈剂量依赖性增加。我们得出结论：1,25-二羟基维生素D3的C-3、C-25和C-1β-D-吡喃葡萄糖苷在体内具有生物活性且效力相同，很可能是由于水解为游离糖苷配基，并且在这方面它们的活性低于糖苷配基。
