Development of a rat parathyroid hormone 2 receptor antagonist

Peptides. 2007 Apr;28(4):887-92. doi: 10.1016/j.peptides.2006.12.002. Epub 2007 Jan 4.

Abstract

The parathyroid hormone 2 (PTH2) receptor is a Family B G-protein coupled receptor most highly expressed within the brain. Current evidence suggests that tuberoinfundibular peptide of 39 residues (TIP39) is the PTH2 receptor's endogenous ligand. To facilitate investigation of the physiological function of the PTH2 receptor/TIP39 system, we have developed a novel PTH2 receptor antagonist, by changing several residues within the amino terminal domain of TIP39. Histidine(4), tyrosine(5), tryptophan(6), histidine(7)-TIP39 binds the PTH2 receptor with high affinity, has over 30-fold selectivity for the rat PTH2 receptor over the rat PTH1 receptor and displays no detectable agonist activity. This ligand should be useful for in vivo investigation of PTH2 receptor function.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cell Line
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Mutagenesis, Site-Directed
  • Mutation
  • Neuropeptides / chemistry
  • Neuropeptides / genetics
  • Neuropeptides / pharmacology*
  • Rats
  • Receptor, Parathyroid Hormone, Type 2 / antagonists & inhibitors*
  • Receptor, Parathyroid Hormone, Type 2 / genetics

Substances

  • Neuropeptides
  • Receptor, Parathyroid Hormone, Type 2
  • tuberoinfundibular peptide 39
  • Cyclic AMP