Refractoriness to phosphaturic action of parathyroid hormone occurring independent of phosphate depletion in hyperparathyroid rats.
In an attempt to clarify the underlying mechanism(s) in the disappearance of phosphaturic response to bolus parathyroid hormone (PTH) in hyperparathyroid patients, the effects of bolus bovine PTH (10 USP U) were studied in conscious thyroparathyroidectomized (T . PTX) male Wistar rats that had been infused with a dose of PTH (2.5 U/hr, for 16 hours) so as to reproduce hyperparathyroidism. These animals responded with an increase in urinary cyclic AMP, but without an increase in renal clearance of phosphate. The loss of phosphaturic response was not prevented by pretreatment with actinomycin D at a dosage close to full toxicity (0.1 mg/kg BW, ip, for 3 days). Actinomycin D at this dosage did not affect the normal stimulatory effects of bolus PTH on urinary cyclic AMP and renal clearance of phosphate in T . PTX rats. The continuous infusion of PTH produced nearly maximal phosphaturia throughout in the face of a significant depletion of phosphate. In addition, pretreatment with actinomycin D did not cause a further increase in urinary phosphate excretion during the infusion. These results, along with the report of Shah et al. (1979) indicating that the development of antiphosphaturic adaptation to acute phosphate depletion was prevented by comparable amounts of actinomycin D, indicate that the disappearance of phosphaturic response to bolus PTH by prior PTH infusion simply signifies the continuation of maximal phosphaturic response to the preceding PTH infusion. It is also suggested that the continuous action of PTH prevents, at least phenomenologically, the development of the gene-activation-mediated refractoriness to PTH or antiphosphaturia induced by acute phosphate depletion.
D000818:Animals; D000242:Cyclic AMP / Q000652:urine; D003609:Dactinomycin / Q000494:pharmacology; D006961:Hyperparathyroidism / Q000378:metabolism*; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000502:physiology*; D010710:Phosphates / Q000097:blood / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D010710:Phosphates; D003609:Dactinomycin; D000242:Cyclic AMP