Effect of dibutyryl cyclic adenosine 3',5'-monophosphate, theophylline, and other nucleotides upon calcium and phosphate metabolism.

The effect of dibutyryl cyclic adenosine 3',5'-monophosphate upon calcium and phosphate metabolism in thyroparathyroidectomized rats was undertaken in an effort to clarify the possible role of adenosine 3',5'-monophosphate (3',5' AMP) in parathyroid hormone action. The infusion of dibutyryl cyclic 3',5' AMP at a rate of 3 mg/hr into thyroparathyroidectomized rats leads to changes in calcium, phosphate, and hydroxyproline excretion, and calcium and phosphate concentrations in plasma that are qualitatively similar to those induced by parathyroid hormone given at a rate of 5 mug/hr. The effect of dibutyryl cyclic 3',5' AMP upon calcium and hydroxyproline mobilization from bone is blocked by thyrocalcitonin administration in the same way that thyrocalcitonin blocks PTH effects. Other closely related nucleotides do not act in the same way. These data indicate that dibutyryl cyclic 3',5' AMP produces effects similar to parathyroid hormone in thyroparathyroidectomized rats, and support the notion that 3',5' AMP is an intermediate in the mechanism of PTH action. However, the changes in magnesium and potassium excretion are different after dibutyryl cyclic 3',5' AMP infusion from those seen after PTH infusion. Also, theophylline was found to potentiate the action of smaller doses of dibutyryl 3',5' AMP, but not that of PTH.