Renal parathyroid hormone receptors in the chick: downregulation in secondary hyperparathyroid animal models.
We characterized the binding of 125I-[Nle8, Nle18, Tyr34]parathyroid hormone-(1-34) amide [125I-nlPTH-(1-34)] to renal plasma membranes prepared from chicks to determine the effects of secondary hyperparathyroid states on renal PTH receptors. This radioligand exhibited specific binding to membranes with high affinity (Kd, 2-3 X 10(-9) M). Agonists or competitive antagonists of PTH were effective in competing for binding sites labeled with 125I-nlPTH-(1-34), whereas an inactive fragment of PTH, salmon calcitonin, and bovine growth hormone did not compete with the radioligand for renal PTH receptors. Newly hatched chicks raised on control diet with adequate vitamin D and calcium or diets deficient in either vitamin D or calcium were used to study the regulation of renal PTH receptors in experimental models of secondary hyperparathyroidism. We found that both experimental diets resulted in marked hypocalcemia and progressive loss of renal cyclic AMP responsiveness to PTH in vitro. Associated with this refractoriness to the hormone was a marked reduction in PTH receptors in membranes from both vitamin D-deficient and calcium-deficient chick kidney. No change in the affinity of the PTH receptors was found. Vitamin D3, in a single dose of 250 micrograms, partially restored serum calcium of vitamin D-deficient birds toward normal by 72 h and also partly restored renal cyclic AMP responsiveness to PTH and the PTH receptor number toward control values. We conclude that renal refractoriness to PTH observed in experimentally hyperparathyroid animals models is due to a marked loss of plasma membrane receptor sites for PTH without an apparent change in the affinity of the receptors for the hormone.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000172:deficiency; D002645:Chickens / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism
D010281:Parathyroid Hormone; D011956:Receptors, Cell Surface; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium