scholarly journals A naturally occurring isoform inhibits parathyroid hormone receptor trafficking and signaling

2010 ◽  
Vol 26 (1) ◽  
pp. 143-155 ◽  
Author(s):  
Verónica Alonso ◽  
Juan A Ardura ◽  
Bin Wang ◽  
W Bruce Sneddon ◽  
Peter A Friedman
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Receptor ◽  
Receptor Trafficking ◽  
Parathyroid Hormone Receptor ◽  
Naturally Occurring

Dissociation of β-Arrestin-Dependent Desensitization and Signaling Using 'Biased' Parathyroid Hormone Receptor Ligands

2019 ◽  
Author(s):  
Kathryn M. Appleton ◽  
Mi-Hye Lee ◽  
Erik G. Strungs ◽  
Carlos Nogueras-Ortiz ◽  
Diane Gesty-Palmer ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Receptor ◽  
Receptor Ligands ◽  
Parathyroid Hormone Receptor

scholarly journals Use of Backbone Modification To Enlarge the Spatiotemporal Diversity of Parathyroid Hormone Receptor-1 Signaling via Biased Agonism

2019 ◽  
Vol 141 (37) ◽  
pp. 14486-14490 ◽  
Author(s):  
Shi Liu ◽  
Frederic G. Jean-Alphonse ◽  
Alex D. White ◽  
Denise Wootten ◽  
Patrick M. Sexton ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Receptor ◽  
Parathyroid Hormone Receptor ◽  
Biased Agonism ◽  
Backbone Modification

scholarly journals Actions of the Small Molecule Ligands SW106 and AH-3960 on the Type-1 Parathyroid Hormone Receptor

2015 ◽  
Vol 29 (2) ◽  
pp. 307-321 ◽  
Author(s):  
Percy H. Carter ◽  
Thomas Dean ◽  
Brijesh Bhayana ◽  
Ashok Khatri ◽  
Raj Rajur ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Small Molecule ◽  
Hormone Receptor ◽  
Transmembrane Domain ◽  
Receptor Activation ◽  
Blood Calcium ◽  
Parathyroid Hormone Receptor ◽  
Peptide Analog ◽  
Amino Terminal ◽  
Small Molecule Ligands

Abstract The parathyroid hormone receptor-1 (PTHR1) plays critical roles in regulating blood calcium levels and bone metabolism and is thus of interest for small-molecule ligand development. Of the few small-molecule ligands reported for the PTHR1, most are of low affinity, and none has a well-defined mechanism of action. Here, we show that SW106 and AH-3960, compounds previously identified to act as an antagonist and agonist, respectively, on the PTHR1, each bind to PTHR1-delNT, a PTHR1 construct that lacks the large amino-terminal extracellular domain used for binding endogenous PTH peptide ligands, with the same micromolar affinity with which it binds to the intact PTHR1. SW106 antagonized PTHR1-mediated cAMP signaling induced by the peptide analog, M-PTH(1–11), as well as by the native PTH(1–9) sequence, as tethered to the extracellular end of transmembrane domain (TMD) helix-1 of the receptor. SW106, however, did not function as an inverse agonist on either PTHR1-H223R or PTHR1-T410P, which have activating mutations at the cytoplasmic ends of TMD helices 2 and 6, respectively. The overall data indicate that SW106 and AH-3960 each bind to the PTHR1 TMD region and likely to within an extracellularly exposed area that is occupied by the N-terminal residues of PTH peptides. Additionally, they suggest that the inhibitory effects of SW106 are limited to the extracellular portions of the TMD region that mediate interactions with agonist ligands but do not extend to receptor-activation determinants situated more deeply in the helical bundle. The study helps to elucidate potential mechanisms of small-molecule binding at the PTHR1.

AUTOANTIBODIES TO PARATHYROID HORMONE RECEPTOR

The Lancet ◽  
1978 ◽  
Vol 312 (8102) ◽  
pp. 1222-1224 ◽  
Author(s):  
H Jüppner ◽  
A.A Bialasiewicz ◽  
R.D Hesch
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Receptor ◽  
Parathyroid Hormone Receptor
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