Impaired Renal Adenylate Cyclase Response to Parathyroid Hormone in the Calcium-Deficient Rat*

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Abstract
The PTH[parathyroid hormone]-dependent adenylate cyclase of rat renal cortex was impaired in the vitamin D-replete animal fed a low Ca diet. Male weanling rats were fed a vitamin D-deficient diet containing either 0.47% Ca (controls) or 0.02% Ca (low Ca) and 0.36% P. Both groups were treated with 70 IU vitamin D2 twice weekly. Circulating immunoreactive PTH was elevated over control levels by 7 days, and by 4 wk was more than 5-fold greater than control. Total serum Ca was decreased by the low Ca diet at all time points studied with a maximum decrease of 2-3 mg/100 ml. The PTH-dependent adenylate cyclase activity of renal cortical membranes prepared from rats fed the low Ca diet exhibited a significant decrease compared to those receiving the control diet. The basal enzyme activity and the stimulation by F-, salmon calcitonin and vasopressin were similar in both groups. In studies with renal cortical slices, control tissue exhibited a 3.5-fold increase in c[cyclic]AMP content over basal levels in the presence of 1 .mu.g PTH/ml, whereas tissue from low Ca animals showed only a 2-fold increase in response to the hormone. The reduction in renal PTH-dependent adenylate cyclase activity of the low Ca animals is due to chronic exposure of target cells to either high circulating PTH, or to the Ca deficiency, or to an interaction between elevated PTH and reduced Ca.