Nomenclature: PTH2 receptor

Family: Parathyroid hormone receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 550 2q33 PTH2R parathyroid hormone 2 receptor 28,31
Mouse 7 546 1 C3 Pth2r parathyroid hormone 2 receptor
Rat 7 546 9q32 Pth2r parathyroid hormone 2 receptor 27
Previous and Unofficial Names
PTHR2
parathyroid hormone receptor 2
parathyroid hormone 2 receptor
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
PTH {Sp: Human} , PTH {Sp: Rat} , PTH {Sp: Mouse}
PTHrP-(1-36) {Sp: Human}
TIP39 {Sp: Human, Bovine} , TIP39 {Sp: Mouse, Rat}
Comments: PTH is a weak partial agonist in rat. PTHrP has very low efficacy.
Rank order of potency (Human)
TIP39 (PTH2, Q96A98), PTH (PTH, P01270) >> PTHrP (PTHLH, P12272)
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I][Nle8,21,Tyr34]PTH-(1-34)-NH2 (rat) Hs Full agonist 8.1 pKd 3
pKd 8.1 [3]
TIP39 {Sp: Mouse, Rat} Hs Full agonist 8.8 pIC50 17
pIC50 8.8 [17]
TIP39 {Sp: Human, Bovine} Hs Full agonist 7.6 – 9.2 pIC50 17,19
pIC50 7.6 – 9.2 [17,19]
PTH-(1-34) (rat) Hs Full agonist 7.2 – 9.5 pIC50 4,17,19
pIC50 7.2 – 9.5 [4,17,19]
TIP39 {Sp: Mouse, Rat} Rn Full agonist 8.1 pIC50 17
pIC50 8.1 [17]
teriparatide Hs Full agonist 7.7 – 7.8 pIC50 16-17
pIC50 7.7 – 7.8 [16-17]
[Ile5,Trp23,Tyr36]PTHrP-(1-36)-NH2 (human) Hs Full agonist 7.7 pIC50 3
pIC50 7.7 [3]
[Ile5,Trp23]PTHrP-(1-36) (human) Hs Full agonist 7.1 – 8.0 pIC50 4,16
pIC50 7.1 – 8.0 [4,16]
[Trp23]PTHrP-(1-36) (human) Hs Full agonist 7.5 pIC50 16
pIC50 7.5 [16]
[Trp23,Tyr36]PTHrP-(1-36)-NH2 (human) Hs Full agonist 7.4 pIC50 3
pIC50 7.4 [3]
[Ile5,Trp23]PTHrP-(2-36) (human) Hs Full agonist 7.3 pIC50 4
pIC50 7.3 [4]
[Ile5,Trp23]PTHrP-(3-36) (human) Hs Full agonist 7.2 pIC50 4
pIC50 7.2 [4]
TIP39 {Sp: Human, Bovine} Rn Full agonist 7.0 pIC50 17
pIC50 7.0 [17]
[Ile5,Trp23]PTHrP-(5-36) (human) Hs Full agonist 7.0 pIC50 4
pIC50 7.0 [4]
[Ile5,Trp23]PTHrP-(4-36) (human) Hs Full agonist 6.8 pIC50 4
pIC50 6.8 [4]
PTH-(1-34) (rat) Rn Full agonist 6.8 pIC50 17
pIC50 6.8 [17]
[His5]PTH-(1-34) (human) Hs Full agonist 6.6 pIC50 16
pIC50 6.6 [16]
[Phe23]PTH-(1-34) (human) Hs Full agonist 6.3 pIC50 16
pIC50 6.3 [16]
teriparatide Rn Full agonist 6.3 pIC50 17
pIC50 6.3 [17]
[Ile5]PTHrP-(1-36) Hs Full agonist 6.2 pIC50 17
pIC50 6.2 [17]
PTHrP-(1-34) Hs Full agonist 6.1 pIC50 17
pIC50 6.1 [17]
PTHrP-(1-36) {Sp: Human} Hs Full agonist 5.7 pIC50 16
pIC50 5.7 [16]
PTHrP-(1-34) Rn Full agonist 5.3 pIC50 17
pIC50 5.3 [17]
View species-specific agonist tables
Agonist Comments
The species of peptide ligand is stated in parentheses. This can include synthetic peptides made based on the sequence of the stated species.

The amino acide sequences of human and bovine TIP39 are identical. Mouse TIP39 differs in four positions at the carboxyl-terminal of the polypeptide.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[His4, Tyr5, Trp6, His7]TIP39 (human) Rn Antagonist 7.61 pA2
pA2 7.61
TIP39-(7-39) (mouse) Hs Antagonist 8.2 pIC50 17
pIC50 8.2 [17]
PTHrP-(1-21)/PTH-(22-34) (human) Hs Antagonist 7.0 – 8.0 pIC50 16-17
pIC50 7.0 – 8.0 [16-17]
[D-Trp12]PTH-(7-34) (bovine) Hs Antagonist 7.3 pIC50 17
pIC50 7.3 [17]
TIP39-(7-39) (human/bovine) Hs Antagonist 7.0 – 7.2 pIC50 17,20
pIC50 7.0 – 7.2 [17,20]
[Ile5,Trp23]PTHrP-(5-36) Hs Antagonist 7.0 pIC50 4
pIC50 7.0 [4]
[D-Trp12,Tyr34]PTH-(7-34) (bovine) Hs Antagonist 6.9 pIC50 20
pIC50 6.9 [20]
PTHrP-(7-34) (human, rat, mouse) Hs Antagonist 6.7 pIC50 20
pIC50 6.7 [20]
TIP39-(7-39) (mouse) Rn Antagonist 6.5 pIC50 17
pIC50 6.5 [17]
[D-Trp12]PTH-(7-34) (bovine) Rn Antagonist 6.3 pIC50 17
pIC50 6.3 [17]
TIP39-(7-39) (human/bovine) Rn Antagonist 6.1 pIC50 17
pIC50 6.1 [17]
PTHrP-(1-21)/PTH-(22-34) (human) Rn Antagonist 5.5 pIC50 17
pIC50 5.5 [17]
View species-specific antagonist tables
Antagonist Comments
The species of peptide ligand is stated in parentheses. This can include synthetic peptides made based on the sequence of the stated species.
Tissue Distribution
Brain: medial prefrontal, insular, and ectorhinal cortices, lateral septal nucleus, bed nucleus of the stria terminalis, fundus striati, amygdala, ventral subiculum, hypothalamus, midline and intralaminar thalamic nuclei, medial geniculate body, periaqueductal gray, ventral tegmental area, superior and inferior colliculi, parabrachial nuclei, locus coeruleus, subcoeruleus and periolivary areas, nucleus of the solitary tract.
Species:  Mouse
Technique:  In situ hybridisation and immunohistochemistry.
References:  14
Pancreas (somatostatin-producing pancreatic islets), thyroid gland (parafollicular cells), gastrointestinal tract (peptide-producing cells in the gastric epithelium, parasympathetic ganglion cells in the submucosal and myenteric plexuses), cardiovascular system (vascular endothelium and smooth muscle), chondrocytes in tracheal cartilage, kidney (near the vascular pole of glomeruli), brain, adrenal medulla, zona glomerulosa of the adrenal cortex, parathyroid gland, pulmonary bronchioles.
Species:  Rat
Technique:  in situ hybridisation.
References:  27
Thyroid parafollicular cells, pancreatic islet D cells, some gastrointestinal peptide synthesising cells.
Species:  Rat
Technique:  Immunohistochemistry.
References:  29
CNS: cerebral cortex, striatum, septum, midline thalamic nuclei, hypothalamus (periventricular and arcuate nuclei), external zone of the median eminence, superficial layers of the caudal spinal trigeminal tract, spinal cord dorsal horn.
Species:  Rat
Technique:  In situ hybridisation and immunohistochemistry.
References:  11,32
CNS: spinal cord and dorsal root ganglia.
Species:  Rat
Technique:  in situ hybridisation.
References:  12
Renal vessels, aorta.
Species:  Rat
Technique:  RT-PCR.
References:  13
Expression Datasets

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
Measurement of cAMP levels in F-11 cells (a fusion of rat DRG neurons expressing the PTH2 receptor and a mouse neuroblastoma cell line).
Species:  Rat
Tissue:  F-11 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  30
Measurement of cAMP levels in COS-7 cells transfected with the human PTH2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  5,18,28,30
Measurement of cAMP levels in COS-7 cells transfected with the rat PTH2 receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  18,30
Measurement of cAMP levels in HEK 293 cells transfected with the human PTH2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  1-2,19,23,26
Measurement of Ca2+ levels in HEK 293 cells transfected with the PTH2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in intracellular Ca2+ concentration.
References:  1-2
Measurement of cell proliferation in HEK 293 cells transfected with the human PTH2 receptor, using an ATP bioluminescence assay.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cell proliferation.
References:  23
Measurement of Ca2+ levels in COS-7 cells transfected with the human PTH2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of Ca2+ mobilisation.
References:  17
Measurement of Ca2+ levels in COS-7 cells transfected with the rat PTH2 receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Stimulation of Ca2+ mobilisation.
References:  17
Physiological Functions
Stimulation of hypothalamic releasing factor secretion
Species:  Rat
Tissue:  Hypothalamic explants
References:  33
Positive inotropy
Species:  Rat
Tissue:  Isolated heart
References:  21
Modulation of nociceptive transmission in the spinal cord
Species:  Mouse
Tissue:  in vivo
References:  12
Supraspinal modulation of nociception
Species:  Mouse
Tissue:  in vivo
References:  10
Modulation of Hypothalamo-Pituitary Adrenal Axis
Species:  Mouse
Tissue:  in vivo
References:  8
Stressor-dependent modulation of anxiety-like behavior and memory performance
Species:  Mouse
Tissue:  in vivo
References:  6,15
Modulation of prolactin section by lactating dams
Species:  Rat
Tissue:  in vivo
References:  7
Facilitation of thermal response to cold exposure
Species:  Mouse
Tissue:  in vivo
References:  9
Supression of arginine vasopressin release
Species:  Rat
Tissue:  in vivo
References:  25
Modulation of renal vessel tone
Species:  Rat
Tissue:  Isolated renal vessels
References:  13
Biologically Significant Variants
Type:  Single nucleotide polymorphism.
Species:  Human
Description:  A Ala225 -> Ser polymorphism may be linked to osteoarthritis.
References:  22
General Comments
See [24] for a study describing the molecular modelling of the interaction between PTH and the PTH1 and PTH2 receptors.
Available Assays
DiscoveRx PathHunter® CHO-K1 PTHR2 β-Arrestin Cell Line (Cat no. 93-0306C2)
PathHunter® eXpress PTHR2 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0306E2CP0M)
more info

REFERENCES

1. Behar V, Nakamoto C, Greenberg Z, Bisello A, Suva LJ, Rosenblatt M, Chorev M. (1996) Histidine at position 5 is the specificity "switch" between two parathyroid hormone receptor subtypes. Endocrinology137: 4217-4224. [PMID:8828480]

2. Behar V, Pines M, Nakamoto C, Greenberg Z, Bisello A, Stueckle SM, Bessalle R, Usdin TB, Chorev M, Rosenblatt M, Suva LJ. (1996) The human PTH2 receptor: binding and signal transduction properties of the stably expressed recombinant receptor. Endocrinology137: 2748-2757. [PMID:8770894]

3. Bergwitz C, Jusseaume SA, Luck MD, Jüppner H, Gardella TJ. (1997) Residues in the membrane-spanning and extracellular loop regions of the parathyroid hormone (PTH)-2 receptor determine signaling selectivity for PTH and PTH-related peptide. J Biol Chem272: 28861-28868. [PMID:9360953]

4. Carter PH, Jüppner H, Gardella TJ. (1999) Studies of the N-terminal region of a parathyroid hormone-related peptide (1-36) analog: receptor subtype-selective agonists, antagonists, and photochemical cross-linking agents. Endocrinology140: 4972-4981. [PMID:10537121]

5. Clark JA, Bonner TI, Kim AS, Usdin TB. (1998) Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors. Mol Endocrinol12: 193-206. [PMID:9482662]

6. Coutellier L, Logemann A, Kuo J, Rusnak M, Usdin TB. (2011) TIP39 modulates effects of novelty-induced arousal on memory. Genes Brain Behav.10 (1): 90-9. [PMID:20796031]

7. Cservenák M, Bodnár I, Usdin TB, Palkovits M, Nagy GM, Dobolyi A. (2010) Tuberoinfundibular peptide of 39 residues is activated during lactation and participates in the suckling-induced prolactin release in rat. Endocrinology151 (12): 5830-40. [PMID:20861230]

8. Dimitrov E, Usdin TB. (2010) Tuberoinfundibular peptide of 39 residues modulates the mouse hypothalamic-pituitary-adrenal axis via paraventricular glutamatergic neurons. J. Comp. Neurol.518 (21): 4375-94. [PMID:20853513]

9. Dimitrov EL, Kim YY, Usdin TB. (2011) Regulation of hypothalamic signaling by tuberoinfundibular peptide of 39 residues is critical for the response to cold: a novel peptidergic mechanism of thermoregulation. J. Neurosci.31 (49): 18166-79. [PMID:22159128]

10. Dimitrov EL, Petrus E, Usdin TB. (2010) Tuberoinfundibular peptide of 39 residues (TIP39) signaling modulates acute and tonic nociception. Exp. Neurol.226 (1): 68-83. [PMID:20696160]

11. Dobolyi A, Irwin S, Wang J, Usdin TB. (2006) The distribution and neurochemistry of the parathyroid hormone 2 receptor in the rat hypothalamus. Neurochem Res31: 227-236. [PMID:16570212]

12. Dobolyi A, Ueda H, Uchida H, Palkovits M, Usdin TB. (2002) Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception. Proc Natl Acad Sci U S A99: 1651-1656. [PMID:11818570]

13. Eichinger A, Fiaschi-Taesch N, Massfelder T, Fritsch S, Barthelmebs M, Helwig JJ. (2002) Transcript expression of the tuberoinfundibular peptide (TIP)39/PTH2 receptor system and non-PTH1 receptor-mediated tonic effects of TIP39 and other PTH2 receptor ligands in renal vessels. Endocrinology143: 3036-3043. [PMID:12130570]

14. Faber CA, Dobolyi A, Sleeman M, Usdin TB. (2007) Distribution of tuberoinfundibular peptide of 39 residues and its receptor, parathyroid hormone 2 receptor, in the mouse brain. J Comp Neurol502: 563-583. [PMID:17394159]

15. Fegley DB, Holmes A, Riordan T, Faber CA, Weiss JR, Ma S, Batkai S, Pacher P, Dobolyi A, Murphy A et al.. (2008) Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues. Genes Brain Behav.7 (8): 933-42. [PMID:18700839]

16. 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 Chem271: 19888-19893. [PMID:8702701]

17. 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 Ther299: 678-690. [PMID:11602681]

18. Hoare SR, Bonner TI, Usdin TB. (1999) Comparison of rat and human parathyroid hormone 2 (PTH2) receptor activation: PTH is a low potency partial agonist at the rat PTH2 receptor. Endocrinology140: 4419-4425. [PMID:10499494]

19. 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 Chem275: 27274-27283. [PMID:10854439]

20. Hoare SR, Usdin TB. (2000) Tuberoinfundibular peptide (7-39) [TIP(7-39)], a novel, selective, high-affinity antagonist for the parathyroid hormone-1 receptor with no detectable agonist activity. J Pharmacol Exp Ther295: 761-770. [PMID:11046116]

21. LaBuda CJ, Dobolyi A, Usdin TB. (2004) Tuberoinfundibular peptide of 39 residues produces anxiolytic and antidepressant actions. Neuroreport15: 881-885. [PMID:15073536]

22. Meulenbelt I, Min JL, van Duijn CM, Kloppenburg M, Breedveld FC, Slagboom PE. (2006) Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Eur J Hum Genet14: 1280-1287. [PMID:16912703]

23. Misiano P, Scott BB, Scheideler MA, Garnier M. (2003) PTH2 receptor-mediated inhibitory effect of parathyroid hormone and TIP39 on cell proliferation. Eur J Pharmacol468: 159-166. [PMID:12754053]

24. Rölz C, Pellegrini M, Mierke DF. (1999) Molecular characterization of the receptor-ligand complex for parathyroid hormone. Biochemistry38 (20): 6397-405. [PMID:10350457]

25. Sugimura Y, Murase T, Ishizaki S, Tachikawa K, Arima H, Miura Y, Usdin TB, Oiso Y. (2003) Centrally administered tuberoinfundibular peptide of 39 residues inhibits arginine vasopressin release in conscious rats. Endocrinology144: 2791-2796. [PMID:12810532]

26. Turner PR, Mefford S, Bambino T, Nissenson RA. (1998) Transmembrane residues together with the amino terminus limit the response of the parathyroid hormone (PTH) 2 receptor to PTH-related peptide. J Biol Chem273: 3830-3837. [PMID:9461563]

27. Usdin TB, Bonner TI, Harta G, Mezey E. (1996) Distribution of parathyroid hormone-2 receptor messenger ribonucleic acid in rat. Endocrinology137: 4285-4297. [PMID:8828488]

28. Usdin TB, Gruber C, Bonner TI. (1995) Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem270: 15455-15458. [PMID:7797535]

29. Usdin TB, Hilton J, Vertesi T, Harta G, Segre G, Mezey E. (1999) Distribution of the parathyroid hormone 2 receptor in rat: immunolocalization reveals expression by several endocrine cells. Endocrinology140: 3363-3371. [PMID:10385434]

30. Usdin TB, Hoare SR, Wang T, Mezey E, Kowalak JA. (1999) TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci2: 941-943. [PMID:10526330]

31. Usdin TB, Modi W, Bonner TI. (1996) Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. Genomics37: 140-141. [PMID:8921382]

32. Wang T, Palkovits M, Rusnak M, Mezey E, Usdin TB. (2000) Distribution of parathyroid hormone-2 receptor-like immunoreactivity and messenger RNA in the rat nervous system. Neuroscience100: 629-649. [PMID:11098126]

33. Ward HL, Small CJ, Murphy KG, Kennedy AR, Ghatei MA, Bloom SR. (2001) The actions of tuberoinfundibular peptide on the hypothalamo-pituitary axes. Endocrinology142: 3451-3456. [PMID:11459790]

To cite this database page, please use the following:

Ted B. Usdin, Alessandro Bisello, Michael Chorev, Peter A. Friedman, Tom Gardella, Harald Jueppner, T. John Martin, Robert A. Nissenson, John Thomas Potts, Jr., Caroline Silve, Jean-Pierre Vilardaga, Rebecca Hills.
Parathyroid hormone receptors: PTH2 receptor. Last modified on 22/08/2013. Accessed on 31/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=332.

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