Infusion of 50 mU/100 g body wt of calcitonin induced a rapid and marked increase of cyclic AMP in calvaria as well as in plasma of thyroparathyroidectomized rats. These changes preceded the decrease in plasma calcium concentration seen after hormone administration. The possible relationship of this stimulation of cyclic AMP accumulation to the hypocalcemic effect of calcitonin was examined under several experimental settings. It was found that a dose of calcitonin sufficient to cause a significant decrease of plasma calcium failed to produce any detectable accumulation cyclic AMP in calvaria, but when high doses of calcitonin were given, there was an apparent correlation between the integrated change of cyclic AMP metabolism and the duration and magnitude of hypocalcemia. Experiments employing the ophylline and imidazole, which alter cyclic AMP metabolism, led to an apparent dissociation between the hypocalcemic effect of calcitonin and its stimulation of cyclic AMP accumulation in bone.
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