Thiazide diuretics do not potentiate cAMP response to parathyroid hormone.
We evaluated the hypothesis that thiazide-induced hypercalcemia reflects potentiation of the cAMP response to parathyroid hormone (PTH) consequent to inhibition of phosphodiesterase in bone and kidney. A panel of thiazide diuretics did inhibit low-Km phosphodiesterase activity from bone homogenates. However, furosemide, a nonthiazide diuretic that does not promote calcium retention, was more potent a phosphodiesterase inhibitor than either chloro- or hydrochlorothiazide (CTZ, HCTZ). Thiazides did not influence basal or PTH-stimulated cAMP levels in incubated calvaria or renal cortical slices. Administration of CTZ or HCTZ to rats for 4 days did not affect basal cAMP, nor did such treatment potentiate the cAMP response in Calvaria to infusion of parathyroid extract in vivo. CTZ, HCTZ, and furosemide increased basal adenylate cyclase from renal cortex but did not affect PTH-stimulated activity. Adenylate cyclase from bone was not affected by thiazides but was inhibited by furosemide. Thiazide treatment potentiated the calcemic response to parathyroid extract in vivo but did not affect the calcemic response to dibutyryl cAMP. We conclude that potentiation of the cAMP response to PTH does not underlie the unique effects of thiazides on calcium metabolism.
D000818:Animals; D001581:Benzothiadiazines; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D000242:Cyclic AMP / Q000494:pharmacology*; D004232:Diuretics; D004357:Drug Synergism; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors; D051381:Rats; D012886:Skull; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D013961:Thyroid Gland / Q000502:physiology
D001581:Benzothiadiazines; D004232:Diuretics; D010281:Parathyroid Hormone; D010726:Phosphodiesterase Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D005665:Furosemide; D000242:Cyclic AMP; D002118:Calcium