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TRH2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 754

Nomenclature: TRH2 receptor

Family: Thyrotropin-releasing hormone receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor: not present in man
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Mouse - 382 8 E1 Trhr2 thyrotropin releasing hormone receptor 2 5
Rat - 352 19q12 Mlnr motilin receptor 2,8
Previous and Unofficial Names Click here for help
TRH-R2 | Trhr2
Database Links Click here for help
Specialist databases
GPCRDB q9ert2_mouse (Mm), q9r297_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
KEGG Gene

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]MeTRH Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Partial agonist 8.5 pKd 12
pKd 8.5 [12]
MeTRH Small molecule or natural product Mm Partial agonist 8.9 pKi 13
pKi 8.9 [13]
TRH {Sp: Human, Mouse, Rat} Peptide Approved drug Click here for species-specific activity table Rn Full agonist 7.4 pKi 4
pKi 7.4 [4]
taltirelin Small molecule or natural product Mm Full agonist 6.9 pKi 13
pKi 6.9 [13]
View species-specific agonist tables
Antagonist Comments
Wang and Gershengorn (1999) show that midazolam is an antagonist at TRH2 [14].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  1,6
Tissue Distribution Click here for help
Brain.
Species:  Mouse
Technique:  Quantitative PCR.
References:  10
Brain.
Species:  Rat
Technique:  in situ hybridization.
References:  9
Functional Assays Click here for help
Measurement of PIP2 hydrolysis and IP levels in cells stimulated by TRH.
Species:  Rat
Tissue:  Cells in culture.
Response measured:  Stimulation of PIP2 degradation and IP formation.
References:  3,7
Measurement of PIP2 hydrolysis and IP levels in cells stimulated by TRH.
Species:  Mouse
Tissue:  Cells in culture.
Response measured:  Stimulation of PIP2 degradation and IP formation.
References:  3,7
Physiological Functions Comments
The functional role of TRH2 remains unclear.
Physiological Consequences of Altering Gene Expression Click here for help
TRH2 receptor knockout mice exhibit normal thyroid function and increased depression and reduced anxiety phenotypes.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11,13
General Comments
Another TRH receptor, TRH2, has been cloned from the rat, mouse and several other species and shares approximately 50% homology with the TRH1 receptor [2,5,8-9]. A human form of the TRH2 receptor has not been found.

It had been thought that TRH2 was the primary mediator of the effects of TRH (and its analogs) in the central nervous system. This idea has recently been shown to be incorrect [13]. TRH1 is the primary mediator of the effects of TRH (and its analogs) in the central nervous system.

TRH2 exhibits higher basal (or constitutive or agonist-independent) signaling activity than TRH1.

References

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1. Aragay AM, Katz A, Simon MI. (1992) The G alpha q and G alpha 11 proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells. J Biol Chem, 267 (35): 24983-8. [PMID:1334076]

2. Cao J, O'Donnell D, Vu H, Payza K, Pou C, Godbout C, Jakob A, Pelletier M, Lembo P, Ahmad S et al.. (1998) Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor. J Biol Chem, 273 (48): 32281-7. [PMID:9822707]

3. Geras-Raaka E, Gershengorn MC. (1987) Measurement of changes in cellular calcium metabolism in response to thyrotropin-releasing hormone. Meth Enzymol, 141: 36-53. [PMID:3110553]

4. Gershengorn MC, Osman R. (1996) Molecular and cellular biology of thyrotropin-releasing hormone receptors. Physiol Rev, 76 (1): 175-91. [PMID:8592728]

5. Harder S, Lu X, Wang W, Buck F, Gershengorn MC, Bruhn TO. (2001) Regulator of G protein signaling 4 suppresses basal and thyrotropin releasing-hormone (TRH)-stimulated signaling by two mouse TRH receptors, TRH-R(1) and TRH-R(2). Endocrinology, 142 (3): 1188-94. [PMID:11181534]

6. Hsieh KP, Martin TF. (1992) Thyrotropin-releasing hormone and gonadotropin-releasing hormone receptors activate phospholipase C by coupling to the guanosine triphosphate-binding proteins Gq and G11. Mol Endocrinol, 6 (10): 1673-81. [PMID:1333052]

7. Imai A, Gershengorn MC. (1987) Measurement of lipid turnover in response to thyrotropin-releasing hormone. Meth Enzymol, 141: 100-1. [PMID:3037241]

8. Itadani H, Nakamura T, Itoh J, Iwaasa H, Kanatani A, Borkowski J, Ihara M, Ohta M. (1998) Cloning and characterization of a new subtype of thyrotropin-releasing hormone receptors. Biochem Biophys Res Commun, 250 (1): 68-71. [PMID:9735333]

9. O'Dowd BF, Lee DK, Huang W, Nguyen T, Cheng R, Liu Y, Wang B, Gershengorn MC, George SR. (2000) TRH-R2 exhibits similar binding and acute signaling but distinct regulation and anatomic distribution compared with TRH-R1. Mol Endocrinol, 14 (1): 183-93. [PMID:10628757]

10. Regard JB, Sato IT, Coughlin SR. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell, 135 (3): 561-71. [PMID:18984166]

11. Sun Y, Zupan B, Raaka BM, Toth M, Gershengorn MC. (2009) TRH-receptor-type-2-deficient mice are euthyroid and exhibit increased depression and reduced anxiety phenotypes. Neuropsychopharmacology, 34 (6): 1601-8. [PMID:19078951]

12. Taylor RL, Burt DR. (1981) Preparation of 3H-[3-M3-His2]TRH as an improved ligand for TRH receptors. Neuroendocrinology, 32 (5): 310-6. [PMID:6264336]

13. Thirunarayanan N, Nir EA, Raaka BM, Gershengorn MC. (2013) Thyrotropin-releasing hormone receptor type 1 (TRH-R1), not TRH-R2, primarily mediates taltirelin actions in the CNS of mice. Neuropsychopharmacology, 38 (6): 950-6. [PMID:23303050]

14. Wang W, Gershengorn MC. (1999) Rat TRH receptor type 2 exhibits higher basal signaling activity than TRH receptor type 1. Endocrinology, 140 (10): 4916-9. [PMID:10499553]

Contributors

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