Determinants of [Arg2]PTH-(1-34) binding and signaling in the transmembrane region of the parathyroid hormone receptor

Endocrinology. 1994 Sep;135(3):1186-94. doi: 10.1210/endo.135.3.8070362.


Previously, we reported that [Arg2]PTH-(1-34) bound to the rat osteosarcoma cell line, ROS 17/2.8, with 2-fold higher apparent affinity than it did to the opossum kidney cell line, OK, yet the analog was only a weak partial agonist for cAMP stimulation with ROS 17/2.8 cells, whereas it was a full cAMP agonist with OK cells. These results suggested that the rat and opossum PTH receptors differ in a region recognized by the hormone's amino-terminus. In this report we show that the cloned PTH receptors derived from ROS 17/2.8 and OK cells, expressed in COS-7 cells, also displayed altered responses to [Arg2]PTH-(1-34). Thus, [Arg2]PTH-(1-34) bound to the cloned rat PTH receptor with 7-fold higher affinity than it did to the cloned opossum PTH receptor, and in cAMP stimulation assays, it was a much weaker agonist with the rat receptor than it was with the opossum receptor. Studies with rat/opossum PTH receptor chimeras suggested that the membrane-spanning region of the receptor contributed to the different binding and signaling responses to [Arg2]PTH-(1-34). Point mutation analysis identified three sites in or near the extracellular ends of transmembrane domains V and VI, which specifically affected [Arg2]PTH-(1-34) binding and signaling.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chimera
  • Molecular Sequence Data
  • Opossums
  • Parathyroid Hormone / metabolism*
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone / physiology*
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Point Mutation
  • Rats
  • Receptors, Parathyroid Hormone / drug effects
  • Receptors, Parathyroid Hormone / genetics
  • Receptors, Parathyroid Hormone / metabolism*
  • Signal Transduction*
  • Teriparatide* / analogs & derivatives*


  • Parathyroid Hormone
  • Peptide Fragments
  • Receptors, Parathyroid Hormone
  • Teriparatide
  • parathyroid hormone (1-34), Arg(2)-