Tachyphylaxis to PTH in the isolated perfused rat kidney: resistance of anticalciuria.
Downregulation of renal responses to amino-terminal 1-34 parathyroid hormone (PTH) was studied in the isolated perfused rat kidney. PTH induced a sigmoid dose-response relationship in phosphate and urinary cAMP excretion over the concentration range 0.2-36 nM. Renal responses to a second maximally phosphaturic PTH concentration following variable initial PTH concentrations showed tachyphylaxis of both phosphate and urinary cAMP excretion but not of decreased calcium excretion. The sigmoid relationship between integrated phosphate and cAMP excretion was shifted to the right during tachyphylaxis. Administration of a maximal phosphaturic PTH dose prevented any effect on phosphate or cAMP excretion of an equivalent or smaller PTH dose administered 1 h later. Anticalciuria, however, was prolonged by the second dose. These studies indicate that downregulation in the kidneys is restricted to the phosphaturic and urinary cAMP responses but not to the anticalciuric response. They also suggest that the nephron site mediating anticalciuria behaves differently with respect to hormone-receptor interactions from those sites mediating phosphaturia.
D000818:Animals; D002118:Calcium / Q000652:urine*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects*; D009318:Natriuresis; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone; D013618:Tachyphylaxis; D019379:Teriparatide; D013997:Time Factors
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D019379:Teriparatide; D010758:Phosphorus; D000242:Cyclic AMP; D002118:Calcium