Parathyroid Hormone GPCR Assays
Overview of Parathyroid Hormone (PTH) Receptors
PTH plays a central role in the regulation of serum calcium and phosphate. PTH signals through PTH receptors. PTH receptors are closely related to various biological systems, including calcium regulation, endochondral bone formation, cell differentiation, and cell proliferation. Research revealed that mutations in the genes encoding these proteins can lead to a variety of diseases. It is worth noting that PTH receptors may provide new targets for the treatment of some diseases, such as osteoporosis, primary hyperparathyroidism, and malignant tumors.
Fig.1 Ligand recognition and second-messenger signaling at PTHR1. (Gardella, 2015)
Distribution and Functions of PTH receptors
PTH receptors are divided into two subtypes: PTHR1 and PTHR2. Each subtype has a different distribution and mediates different biological effects. PTHR1 is highly expressed in the kidney and bone and is involved in the regulation of calcium metabolism and the homeostasis of inorganic phosphate. PTHR2 is abundantly expressed in the cardiovascular, gastrointestinal system, central nervous system, and testis, and may be related to spermatogenesis and pain perception.
Receptor Signaling
Activated PTH receptors primarily signal through the alpha subunit of G proteins, but they can also activate many other second messenger cascades.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| PTHR1 | PTH1R |
|
|
|
| PTHR2 | PTH2R |
|
|
|
Assay List of Parathyroid Hormone Receptors
Creative Biolabs can provide a range of assays of parathyroid hormone receptors. You can choose the assay in the list or contact us for more information:
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| cAMP Assay | ||||
| S01YF-0722-KX183 | Magic™ Human PTH2R In Vitro cAMP Assay & Reporter Assay, HEK293-CRE-βla | HEK293-CRE-βla | cAMP Assay; Reporter Assay | |
Published Data
| Paper Title |
High-resolution crystal structure of parathyroid hormone 1 receptor in complex with a peptide agonist |
| Journal |
Nature Structural & Molecular Biology |
| Published | 2018 |
| Abstract |
PTH1R is a class B multi-domain GPCR that plays an important role in the regulation of calcium homeostasis. Two endogenous peptide ligands, PTH and parathyroid hormone-related protein (PTHrP), are effective in activating the receptor. Activation of PTH1R is associated with the binding of peptide ligands to the extracellular domain (ECD) and transmembrane domain (TMD) of the receptor. The investigators demonstrated the crystal structure of human PTH1R in complex with a peptide agonist, which allowed them to reveal molecular details in conserved structural motifs critical to class B receptor function. Therefore, this study provided a basis for structural insights into PTH1R function and extends our understanding of the class of GPCRs of therapeutic interest. |
| Result |
Since the peptide ligands of class B receptors are closely related to many fundamental physiological processes, class B GPCRs are potential drug targets for many chronic human diseases. Recombinant analogs of PTH and PTHrP are critical in the treatment of severe osteoporosis. The crystal structure of human PTH1R in complex with a peptide agonist provides a new basis for understanding the molecular structure of this receptor, which provides opportunities for future use of this structure as a design of new chemical entities.
|
Fig.2 Structural and functional details of PTH1R-ePTH interactions. (Ehrenmann, 2018)
References
- Gardella, T. J.; Vilardaga, J. P. International union of basic and clinical pharmacology. XCIII. The parathyroid hormone receptors-family BG protein-coupled receptors. Pharmacological Reviews. 2015; 67(2): 310-337.
- Ehrenmann, J.; et al. High-resolution crystal structure of parathyroid hormone 1 receptor in complex with a peptide agonist. Nature Structural & Molecular Biology. 2018; 25(12): 1086-1092.
