title: Specificity and stability of a new PTH1 receptor antagonist, mouse TIP(7-39).
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.
authors.affiliation: Unit on Cell Biology, National Institute of Mental Health, Room 3D06, Bld. 36, 36 Convent Drive, Bethesda, MD 20892-4092, USA.
authors.forename: Sam R J
authors.initials: SR
authors.lastname: Hoare
authors.forename: Ted B
authors.initials: TB
authors.lastname: Usdin
mesh_terms: D000818:Animals; D019556:COS Cells; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D051379:Mice; D009479:Neuropeptides / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D018016:Receptors, Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D014162:Transfection
chemical_list: D009479:Neuropeptides; D010446:Peptide Fragments; D018016:Receptors, Parathyroid Hormone; C400136:tuberoinfundibular peptide 39; D000242:Cyclic AMP