Parathyroid hormone-1 receptor down-regulation in kidneys from rats with chronic renal failure.
Although secondary hyperparathyroidism is a common complication of chronic renal failure, few studies have examined the characteristics of parathyroid hormone (PTH) binding to the kidney or the regulation of the PTH receptor in chronic renal disease. In this study we measured PTH binding to the PTH-1 receptor in renal cortical membranes from normal rats and from rats with experimentally induced chronic renal failure. In normal rats, analysis of saturation binding experiments using 125I PTH-related peptide (chicken, cPTHrP) revealed apparent Kd and Bmax values of 1.16 +/- 0.14 nmol/l and 338 +/- 22.7 fmol/mg, respectively. Three weeks following induction of renal failure there was no change in the affinity of the PTH-1 receptor (Kd = 1.51 +/- 0.24 nmol/l) but the Bmax was reduced by 45% (183 +/- 32.5). In normal rats which had undergone thyroparathyroidectomy, the Kd was unchanged (1.17 +/- 0.09) while the Bmax increased to 459 +/- 31 fmol/mg. We conclude that chronic renal failure is accompanied by a downregulation of renal PTH-1 receptors.
Edwards
R M
RM
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa 19406 0939, USA. Richard_M_Edwards@sbphrd.com
Contino
L C
LC
Gellai
M
M
Brooks
D P
DP
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D018016:Receptors, Parathyroid Hormone