Binding properties of plasma vitamin D-binding protein and intestinal 1,25-dihydroxyvitamin D3 receptor in piglets with pseudo-vitamin D-deficiency rickets, type I: treatment effects with pharmacological doses of vitamin D3.
The effective treatment of the rachitic symptoms of pseudo-vitamin D-deficiency rickets, type I (PVDRI) by massive doses of vitamin D3 was examined. For this purpose, the affinities and the maximum binding capacities (Bmax) of the plasma vitamin D-binding protein (DBP) and of the intestinal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptor for vitamin D3, 25-hydroxyvitamin D3 (25-OHD3) and 1,25-(OH)2D3, were investigated in normal piglets and in rachitic piglets that suffered from PVDRI. The piglets were 5 to 10 weeks old and of both sexes. The Bmax of plasma DBP for 25-OHD3 was 6.77 +/- 0.45 microM for PVDRI piglets and 7.30 +/- 0.41 microM for control piglets and showed no differences between the two groups. Equilibrium association constants (Ka) of DBP for 25-OHD3 were 4.3 x 10(8) M-1 for PVDRI piglets and 4.0 x 10(8) M-1 for controls and showed also no differences between the two groups. Similarly the Ka of DBP for 1,25-(OH)2D3 was also the same for rachitic and control piglets (1.45 x 10(7) and 1.54 x 10(7) M-1, respectively). Due to the lower circulating concentration of 1,25-(OH)2D3 in the plasma of rachitic piglets compared to that of controls its free metabolite index was significantly lower in rachitic (0.42 +/- 0.05 x 10(-5)) than in control piglets (3.63 +/- 0.30 x 10(-5)). The Kd and Bmax of the intestinal nuclear receptor for 1,25-(OH)2D3 of rachitic and control piglets were 0.31 +/- 0.05 and 0.33 +/- 0.05 nM and 674 +/- 103 and 719 +/- 123 fmol/mg protein, respectively, and were also not different between the two groups of piglets. It was concluded from these observations that the rachitic symptoms of PVDRI piglets resulted solely from the lower free 1,25-(OH)2D3 concentration in plasma compared to that of normal piglets. The relative affinities of the intestinal 1,25-(OH)2D3 receptor for vitamin D3 and 25-OHD3 were also measured. It was found that 50% displacement of 1,25-(OH)2D3 from the intestinal receptor of PVDRI and control piglets required a 220,000- and 245,000-fold excess of the free concentration of vitamin D3, respectively, and a 20- to 42- and 23- to 71-fold excess of the free concentration of 25-OHD3, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Kaune
R
R
Department of Physiology, School of Veterinary Medicine, Hannover, FRG.
Schroeder
B
B
Harmeyer
J
J
D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D012279:Rickets / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000378:metabolism*
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D014809:Vitamin D-Binding Protein; D002762:Cholecalciferol; D002117:Calcitriol; D002112:Calcifediol