Parathyroid hormone-mediated refractoriness of rat kidney cyclic AMP system.

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Abstract
The effects of acute treatment of rats with parathyroid hormone (PTH) were studied on the subsequent responsiveness of the renal adenylate cyclase [AC] system to stimulation by PTH. Infusion of 175 U [units] of PTH/kg body wt per hour for 8 h produced a decrease both in the in vitro cyclic[c]AMP response of cortical slices to PTH and in the PTH-dependent AC activity of cortical membranes. A single dose of 100 U of PTH/kg had no such effect. The PTH-mediated refractoriness of the cAMP system was reversed 4 h after discontinuation of the hormone infusion. A direct effect of PTH on the kidney was demonstrated: incubation of cortical tissue with 25 .mu.g PTH/ml resulted in a similar decrease in PTH-dependent AC activity. Acute infusion of rats with the hormone also decreased the responsiveness of the enzyme to activation by calcitonin and F- but not by vasopressin. Thyroparathyroidectomized rats were also refractory to calcitonin, indicating that PTH was acting to decrease the calcitonin-dependent AC activity independent of the secondary elevation of circulating calcitonin that was noted in the intact rat infused with PTH. Acute infusion of PTH is associated with subsequent inhibition of the catalytic activity of the AC and an additional reduction in the receptor-mediated activation of the enzyme by PTH and calcitonin.

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