Paradoxical response to parathyroid hormone of renal handling of phosphate in hyperparathyroid rats.
The effect of PTH given as a bolus on renal handling of phosphate in rats was studied by a perfusion balance study method. In vitamin D-fed rats, iv PTH as a bolus (10 USP units) elicited a phosphaturic response and an increase in urinary cAMP, whether or not the rats were thyroparathyroidectomized. When given to thyroparathyroidectomized rats receiving continuous infusion of PTH (2.5 USP units/h) for 16 h, PTH led to a paradoxical decline of phosphate clearance in spite of an increase in urinary cAMP. Vitamin D-deficient intact rats also showed this paradoxical response. Vitamin D-deficient thyroparathyroidectomized rats showed an ordinary phosphaturic response. When PTH had been supplied continuously (2.5 USP units/h) to these rats, the PTH bolus again produced the paradoxical response. Phosphate supplementation did not restore the phosphaturic response. (Bu)2cAMP infusion reproduced the paradoxical effect in vitamin D-fed, thyroparathyroidectomized rats receiving continuous infusion of PTH. These data indicate that a long-lasting excess of circulating PTH alters the nature of the response of the kidney to an iv bolus of PTH, so that PTH leads to a paradoxical decline of phosphate clearance, and that the mechanism responsible for the paradox may lie in a step (or steps) subsequent to cAMP production.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000652:urine; D006961:Hyperparathyroidism / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy; D014808:Vitamin D Deficiency / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D010758:Phosphorus; D003994:Bucladesine; D000242:Cyclic AMP; D002118:Calcium