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Gene and Protein Information | ||||||
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 |
TRH-R2 | Trhr2 |
Database Links | |
Specialist databases | |
GPCRdb | q9ert2_mouse (Mm), q9r297_rat (Rn) |
Other databases | |
Ensembl Gene | ENSMUSG00000039079 (Mm), ENSRNOG00000012789 (Rn) |
Entrez Gene | 170732 (Mm), 252859 (Rn) |
KEGG Gene | mmu:170732 (Mm), rno:252859 (Rn) |
Download all structure-activity data for this target as a CSV file
Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific agonist tables |
Antagonist Comments | ||
Wang and Gershengorn (1999) show that midazolam is an antagonist at TRH2 [14]. |
Primary Transduction Mechanisms | |
Transducer | Effector/Response |
Gq/G11 family | Phospholipase C stimulation |
References: 1,6 |
Tissue Distribution | ||||||||
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Functional Assays | ||||||||||
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Physiological Functions Comments | |
The functional role of TRH2 remains unclear. |
Physiological Consequences of Altering Gene Expression | ||||||||||
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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. |
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]