Specificity and stability of a new PTH1 receptor antagonist, mouse TIP(7-39)

Peptides. 2002 May;23(5):989-98. doi: 10.1016/s0196-9781(02)00023-2.

Abstract

Parathyroid hormone 1 (PTH1) receptor antagonists might be of benefit in hypercalcemia of malignancy (HHM) and hyperparathyroidism. We previously identified bovine tuberoinfundibular peptide (7-39) (bTIP(7-39)) as a high-affinity PTH1 receptor antagonist. Mouse TIP(7-39) is an antagonist (rPTH1 K(B)=44 nM, rPTH2=940 nM) that is more potent than other known PTH1 receptor antagonists: bTIP(7-39) (210 nM), PTH-related protein (PTHrP)(7-34) (640 nM), and bPTH(7-34) (>3000 nM). Plasma proteases slowly (t(1/2)=81 min) inactivated [125I] mTIP(7-39). Intravenous plasma [125I]mTIP(7-39) was bi-phasically cleared (radioactivity t(1/2)=2.9 min (70%) and 120 min (30%), binding activity t(1/2)=3.6 min (92%), and t(1/2)=21 min (8%)). Loss of unlabeled mTIP(7-39) (250 microg/kg i.v.) receptor binding was similar. mTIP(7-39)'s high-affinity should facilitate animal evaluation of effects of PTH1 receptor antagonism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Cattle
  • Cyclic AMP / metabolism
  • Half-Life
  • Humans
  • Mice
  • Neuropeptides / blood
  • Neuropeptides / chemistry*
  • Neuropeptides / pharmacokinetics
  • Neuropeptides / pharmacology*
  • Peptide Fragments / blood
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacokinetics
  • Peptide Fragments / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Parathyroid Hormone / antagonists & inhibitors*
  • Receptors, Parathyroid Hormone / genetics
  • Receptors, Parathyroid Hormone / metabolism
  • Sensitivity and Specificity
  • Transfection

Substances

  • Neuropeptides
  • Peptide Fragments
  • Receptors, Parathyroid Hormone
  • tuberoinfundibular peptide 39
  • Cyclic AMP