title: Biological activity of the C-1, C-3, C-25, beta-D-glucopyranosides of 1,25-dihydroxyvitamin D3.
abstract: 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.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats
chemical_list: D005960:Glucosides; D006027:Glycosides; D002117:Calcitriol; D002118:Calcium