title: A dual mechanism for regulation of kidney phosphate transport by parathyroid hormone.
abstract: Regulation of phosphate transport by parathyroid hormone (PTH) was investigated in continuous lines of kidney cells. Phosphate transport was reduced by PTH-(1-34) at physiological concentrations (EC50 5 X 10(-11) M), whereas much higher concentrations were required to stimulate cAMP formation (EC50 1 X 10(-8) M) in opossum kidney (OK) cells. The PTH analogue [Nle]PTH-(3-34) also inhibited phosphate transport but did not enhance cAMP formation. Instead, [Nle]PTH-(3-34) was a competitive antagonist of PTH-(1-34) at cyclase-coupled receptors. PTH-(7-34) had no effect on phosphate transport or cAMP formation. Phorbol esters or mezerein were potent inhibitors of phosphate transport but did not affect cAMP synthesis. Their potencies paralleled the rank-order potency of these agents as activators of protein kinase c in other systems. Maximally effective concentrations of PTH-(1-34) and mezerein did not produce additive inhibition of phosphate transport in OK cells. Phorbol esters stimulated phosphate transport in JTC-12 cells, but PTH-(1-34) had no effect. We concluded that PTH regulates OK cell phosphate transport by interacting with two classes of receptors, and transmembrane-signaling mechanisms. Physiological levels of PTH-(1-34) may regulate phosphate transport by activation of protein kinase c, whereas higher concentrations appear to activate adenylate cyclase.
mesh_terms: D001692:Biological Transport; D001696:Biomechanical Phenomena; D002460:Cell Line; D004224:Diterpenes; D004347:Drug Interactions; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D013729:Terpenes; C025076:parathyroid hormone (1-34), bovine; C011309:mezerein; D012964:Sodium