Inhibition of 25-hydroxyvitamin D3-1-hydroxylase by chronic metabolic acidosis.
Chronic metabolic acidosis had been shown to influence the renal metabolism of 25-hydroxyvitamin D3. Using the isolated perfused rat kidney model, we evaluated the rates of synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in vitamin D-depleted [D(-)] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in vitamin D-replete [D(+)] rats. Metabolic acidosis was induced in both groups of rats by feeding aqueous ammonium chloride for 9 days. Kidneys isolated from D(-) acidotic rats (mean pH, 7.11) exhibited a decreased rate of 1,25(OH)2D3 synthesis (0.79 +/- 0.17 pmol produce . h-1 . g kidney-1) when compared with that (1.27 +/- 0.09) of D(-) nonacidotic (mean pH, 7.33) rats. There was a significant negative linear correlation between the rate of synthesis of 1,25(OH)2D3 and the hydrogen ion concentration of the animal (r = 0.79, P less than 0.005). The rate of synthesis of 24,25(OH)2D3 by the kidneys from D(+) acidotic (mean pH, 7.06) and nonacidotic (mean pH, 7.39) rats did not differ (0.81 +/- 0.21 vs. 0.60 +/- 0.12 pmol product . h-1 . g kidney-1). It is concluded that chronic acidosis suppressed 1-hydroxylase activity, but does not suppress 24-hydroxylase activity.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D000138:Acidosis / Q000201:enzymology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002908:Chronic Disease; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D014808:Vitamin D Deficiency / Q000201:enzymology*
D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium