Effect of chlorpropamide on renal response to parathyroid hormone in normal subjects and in patients with hypoparathyroidism and pseudohypoparathyroidism

Chlorpropamide inhibited by 35 to 65% the increase in the urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) following a large dose (250 U) of parathyroid hormone (PTH) in normal subjects and patients with hypoparathyroidism and pseudohypoparathyroidism. By contrast, in normal subjects, the response of urinary cyclic AMP excretion to smaller amounts of PTH (15 and 30 U) was not decreased by chlorpropamide. Chlorpropamide did not decrease the phosphaturic response to any dose of PTH. The probable explanation for the discrepant effects of chlorpropamide on urinary cyclic AMP and phosphate excretions is that phosphaturia results from a minimal elevation of cyclic AMP and that chlorpropamide does not decrease cyclic AMP production to such a low level. Chlorpropamide decreased the accumulation of renal cyclic AMP in response to PTH in the parathyroidectomized rat, suggesting that this may be the mechanism of action for this drug in decreasing the urinary excretion of cyclic AMP in response to PTH in man. Tolazamide, another sulfonylurea, did not inhibit the elevation of urinary cyclic AMP excretion after PTH. Therefore, the sulfonylurea part of the molecule is probably not involved in the inhibition produced by chlorpropamide.