Biological activity assessment of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone in the rat.
1 alpha,25-Dihydroxyvitamin D3-26,23-lactone [1 alpha,25(OH)2D3-26,23-lactone] was compared to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in terms of their stimulation, in vivo, of intestinal calcium transport and mobilization of calcium from bone in the rat (the two classic vitamin D-mediated responses), and their relative binding to the chick intestinal receptor for 1 alpha,25(OH)2D3, 1 alpha,25-(OH)2D3-26,23-lactone was found to be only one-thirtieth as active as 1 alpha,25-(OH)2D3 in the stimulation of intestinal calcium transport and was found to mediate a significant reduction in the steady-state serum calcium levels. Associated with the reduction in serum calcium was a significant increase in urinary calcium excretion for 24 h after the administration of the steroid. Prior administration of 1 alpha,25(OH)2D3-26,23-lactone partially blocked the actions of a subsequently administered dose of 1 alpha,25(OH)2D3 in increasing serum calcium levels, but did not affect the action of 1 alpha,25(OH)2D3 in stimulating intestinal calcium transport. The binding affinity of 1 alpha,25(OH)2D3-26,23-lactone to the chick intestinal cytosol receptor protein was observed to be 670 times lower than that of 1,25-(OH)2D3 which indicates that perturbation of the 25-hydroxylated side chain by formation of the 26,23-lactone causes a significant reduction in ligand affinity for the receptor.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C026947:1,25-dihydroxyvitamin D3-26,23-lactone; D002117:Calcitriol; D002118:Calcium