Impaired homologous upregulation of vitamin D receptor in rats with chronic renal failure.
We studied the homologous regulation of the vitamin D receptor (VDR) in the duodenum of rats with chronic renal failure. Mean basal nuclear 3H-labeled 1 alpha,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) binding capacity was 48 and 43 fmol/mg protein for sham-operated and uremic rats with similar dissociation constants (Kd), respectively. These results coincided with those of immunoblot analysis, which found that VDR protein level of uremic rats was 87.6% that of sham-operated rats. In uremic rats, 1,25(OH)2D3, 2.0 micrograms/kg, failed to upregulate VDR protein levels until 24 h, in contrast to the significant increases produced in sham-operated rats at both 12 (1.55-fold) and 24 h (1.75-fold). Baseline level of VDR mRNA in uremic rats, determined by Northern blot analysis, was comparable to that in sham-operated rats. Treatment with 1,25(OH)2D3 slightly decreased VDR mRNA at 6-24 h in the sham-operated rats, in contrast to the increase seen at 6 h in uremic rats. These results suggest that the homologous upregulation of VDR was attenuated in rats with chronic renal failure because of an impairment at a translational and/or posttranslational step.
Koyama
H
H
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
Nishizawa
Y
Y
Inaba
M
M
Hino
M
M
Prahl
J M
JM
DeLuca
H F
HF
Morii
H
H
D000704:Analysis of Variance; D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002467:Cell Nucleus / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000096:biosynthesis / Q000378:metabolism*; D012016:Reference Values; D013997:Time Factors; D015854:Up-Regulation; D014511:Uremia / Q000097:blood / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol; D002118:Calcium