The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [4]) are family B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (PTH, P01270) (84 amino acids), and PTHrP (PTHLH, P12272) (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36) (PTHLH, P12272)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (PTH2, Q96A98) (39 amino acids). [¹²⁵I]PTH may be used to label both PTH1 and PTH2 receptors.

The parathyroid hormone type 1 receptor (PTHR) is the canonical GPCR for PTH and PTHrP. It is coupled to G_s and G_q and regulates the development of bone, heart, mammary glands and other tissues in response to PTHrP, and blood concentrations of calcium and phosphate ions, as well as vitamin D, in response to PTH. Another important action of the PTH/PTHR system is to stimulate bone formation when the hormone is intermittently administrated (daily injection).

Although PTH (PTH, P01270) is an agonist at human PTH2 receptors, it fails to activate the rodent orthologues. TIP39 (PTH2, Q96A98) is a weak antagonist at PTH1 receptors [7].

* Key recommended reading is highlighted with an asterisk

* Cheloha RW, Gellman SH, Vilardaga JP, Gardella TJ. (2015) PTH receptor-1 signalling-mechanistic insights and therapeutic prospects. Nat Rev Endocrinol, 11 (12): 712-24. [PMID:26303600]

* Gardella TJ, Vilardaga JP. (2015) International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors-Family B G Protein-Coupled Receptors. Pharmacol. Rev., 67 (2): 310-37. [PMID:25713287]

* Vilardaga JP, Jean-Alphonse FG, Gardella TJ. (2014) Endosomal generation of cAMP in GPCR signaling. Nat. Chem. Biol., 10 (9): 700-6. [PMID:25271346]

1. Gardella TJ, Luck MD, Fan MH, Lee C. (1996) Transmembrane residues of the parathyroid hormone (PTH)/PTH-related peptide receptor that specifically affect binding and signaling by agonist ligands. J. Biol. Chem., 271 (22): 12820-5. [PMID:8662729]

2. Gardella TJ, Luck MD, Jensen GS, Usdin TB, Jüppner H. (1996) Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-2 receptor agonist. J. Biol. Chem., 271 (33): 19888-93. [PMID:8702701]

3. Gardella TJ, Luck MD, Wilson AK, Keutmann HT, Nussbaum SR, Potts Jr JT, Kronenberg HM. (1995) Parathyroid hormone (PTH)-PTH-related peptide hybrid peptides reveal functional interactions between the 1-14 and 15-34 domains of the ligand. J. Biol. Chem., 270 (12): 6584-8. [PMID:7896796]

4. Gardella TJ, Vilardaga JP. (2015) International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors-Family B G Protein-Coupled Receptors. Pharmacol. Rev., 67 (2): 310-37. [PMID:25713287]

5. Goold CP, Usdin TB, Hoare SR. (2001) Regions in rat and human parathyroid hormone (PTH) 2 receptors controlling receptor interaction with PTH and with antagonist ligands. J. Pharmacol. Exp. Ther., 299 (2): 678-90. [PMID:11602681]

6. Hoare SR, Clark JA, Usdin TB. (2000) Molecular determinants of tuberoinfundibular peptide of 39 residues (TIP39) selectivity for the parathyroid hormone-2 (PTH2) receptor. N-terminal truncation of TIP39 reverses PTH2 receptor/PTH1 receptor binding selectivity. J. Biol. Chem., 275 (35): 27274-83. [PMID:10854439]

7. Jonsson KB, John MR, Gensure RC, Gardella TJ, Jüppner H. (2001) Tuberoinfundibular peptide 39 binds to the parathyroid hormone (PTH)/PTH-related peptide receptor, but functions as an antagonist. Endocrinology, 142 (2): 704-9. [PMID:11159842]