Specificity and stability of a new PTH1 receptor antagonist,mouse TIP(7-39) |
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Authors: | Hoare Sam R J Usdin Ted B |
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Affiliation: | Unit on Cell Biology, National Institute of Mental Health, Room 3D06, Bld. 36, 36 Convent Drive, Bethesda, MD 20892-4092, USA. |
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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. |
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