24R,25-dihydroxyvitamin D3 regulates 1,25-dihydroxyvitamin D3 binding to its chick intestinal receptor.
We have studied the binding of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to its crude chromatin chick intestinal receptor in the absence or presence of a ten-fold excess of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] for each concentration of [3H]-1,25(OH)2D3 studied. We have found a significant shift to the right in the binding of 1,25(OH)2D3 to its receptor in the presence of this excess of 24R,25(OH)2D3. As a result, the affinity was found to be significantly reduced, the apparent dissociation constants varied from 0.97 +/- 0.09 (n = 5) to 1.36 +/- 0.04 nM (p less than 0.01). This reduction was related to a significant decrease in the positive cooperativity for the apparent Hill coefficient from nH = 1.49 +/- 0.06 to nH = 1.26 +/- 0.06 (p less than 0.03) in the binding of 1,25(OH)2D3 to its receptor. There was no significant change in the capacity of the receptor (189 +/- 11 compared to 200 +/- 9 fmoles/mg protein). These results suggest that the intestinal 1,25(OH)2D3 receptor must also have a binding recognition site for 24R,25(OH)2D3 which is postulated to play a regulatory role in the 1,25(OH)2D3 receptor's ligand binding properties.
Wilhelm
F
F
Norman
A W
AW
D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D002645:Chickens; D002843:Chromatin / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism*; D007700:Kinetics; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*
D002843:Chromatin; D004100:Dihydroxycholecalciferols; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol