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.
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