Inhibition of the hypercalcemic action of vitamin ds with imidazole

The effects of imidazole on serum calcium were examined in groups of normal and thyroparathyroidectomized (TPTX) rats given a calcium-deficient diet. The TPTX animals had been given either no treatment or vitamin D₃ in doses sufficient to produce a normal or elevated serum calcium. Imidazole lowered the mean serum calcium in each group except the TPTX one which had not received any vitamin D₃ and had hypocalcemia. Studies carried out in vivo with ⁴⁵Ca suggested that imidazole inhibited release of calcium from skeletal tissue. Increases in serum calcium produced with vitamin D₃ were further augmented with theophylline and dibutyryl 3′, 5′- adenosine monophosphate. The increases in serum calcium with these two agents were diminished or prevented with imidazole. In tissue culture studies, imidazole diminished the release of ⁴⁵Ca from untreated fetal rat bone as well as from bones in which resorption was stimulated by 25- hydroxycholecalciferol, dibutyryl 3′, 5′-adenosine monophosphate, and parathyroid hormone. The possible relationship between cyclic 3′, 5′-adenosine monophosphate and vitamin D₃, as regards the calcemic action of the vitamin, is discussed.