Mas1, BB<sub>3</sub>/Brs3, GPR17 | G protein-coupled receptors

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Mas1, BB₃/Brs3, GPR17 C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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These 3 orphan GPCRs are considered 'foster children' of well established GPCR families and are reviewed by the corresponding subcommittee members; Mas1 (Angiotensin receptors), BB₃ receptor (Bombesin receptors), GPR17 (P2Y receptors/Leukotriene receptors).

Receptors

MAS1 C Show summary »« Hide summary More detailed page go icon to follow link

BB₃ receptor C Show summary »« Hide summary More detailed page go icon to follow link

GPR17 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

Nomenclature

GPR17

Previous and unofficial names

P2Y-like receptor | UDP/CysLT receptor | R12 | uracil nucleotide/cysteinyl leukotriene receptor

Genes

GPR17 (Hs), Gpr17 (Mm), Gpr17 (Rn)

Ensembl ID

ENSG00000144230 (Hs), ENSMUSG00000052229 (Mm), ENSRNOG00000065480 (Rn)

UniProtKB AC

Q13304 (Hs), Q6NS65 (Mm), Q09QM4 (Rn)

Principal transduction

G_i/G_o family

Endogenous agonists

LTC₄ [4]

LTD₄ [4]

UDP-glucose [1,4]

UDP-galactose [1,4]

UDP [1,4]

Comment

Reported to be a dual leukotriene and UDP receptor [4]. Another group instead proposed that GPR17 functions as a negative regulator of the CysLT₁ receptor response to leukotriene D₄ (LTD₄). For further discussion, see [5]. Reported to antagonize CysLT₁ receptor signalling in vivo and in vitro [10]. See reviews [2] and [5].

References

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1. Benned-Jensen T, Rosenkilde MM. (2010) Distinct expression and ligand-binding profiles of two constitutively active GPR17 splice variants. Br J Pharmacol, 159 (5): 1092-105. [PMID:20148890]

2. Bäck M, Powell WS, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE. (2014) Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7. Br J Pharmacol, 171 (15): 3551-74. [PMID:24588652]

3. Chobanian HR, Guo Y, Liu P, Chioda M, Lanza Jr TJ, Chang L, Kelly TM, Kan Y, Palyha O, Guan XM et al.. (2012) Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity. ACS Med Chem Lett, 3 (3): 252-6. [PMID:24900461]

4. Ciana P, Fumagalli M, Trincavelli ML, Verderio C, Rosa P, Lecca D, Ferrario S, Parravicini C, Capra V, Gelosa P, Guerrini U, Belcredito S, Cimino M, Sironi L, Tremoli E, Rovati GE, Martini C, Abbracchio MP. (2006) The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J, 25 (19): 4615-27. [PMID:16990797]

5. Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR et al.. (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev, 65 (3): 967-86. [PMID:23686350]

6. Gironacci MM, Adamo HP, Corradi G, Santos RA, Ortiz P, Carretero OA. (2011) Angiotensin (1-7) induces MAS receptor internalization. Hypertension, 58 (2): 176-81. [PMID:21670420]

7. Guan XM, Chen H, Dobbelaar PH, Dong Y, Fong TM, Gagen K, Gorski J, He S, Howard AD, Jian T et al.. (2010) Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity. Cell Metab, 11 (2): 101-12. [PMID:20096642]

8. He S, Dobbelaar PH, Liu J, Jian T, Sebhat IK, Lin LS, Goodman A, Guo C, Guzzo PR, Hadden M et al.. (2010) Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists. Bioorg Med Chem Lett, 20 (6): 1913-7. [PMID:20167483]

9. Lu J, Wu L, Zhu J, Zhou H, Fang M, Liang H, Guo M, Chen M, Zhu Y, Wang J et al.. (2025) Identification of a Novel Antagonist of BRS-3 from Natural Products and Its Protective Effects Against H₂O₂-Induced Cardiomyocyte Injury. Int J Mol Sci, 26 (6). [PMID:40141387]

10. Maekawa A, Balestrieri B, Austen KF, Kanaoka Y. (2009) GPR17 is a negative regulator of the cysteinyl leukotriene 1 receptor response to leukotriene D4. Proc Natl Acad Sci USA, 106 (28): 11685-90. [PMID:19561298]

11. Mantey SA, Coy DH, Entsuah LK, Jensen RT. (2004) Development of bombesin analogs with conformationally restricted amino acid substitutions with enhanced selectivity for the orphan receptor human bombesin receptor subtype 3. J Pharmacol Exp Ther, 310 (3): 1161-70. [PMID:15102928]

12. Mantey SA, Weber HC, Sainz E, Akeson M, Ryan RR, Pradhan TK, Searles RP, Spindel ER, Battey JF, Coy DH et al.. (1997) Discovery of a high affinity radioligand for the human orphan receptor, bombesin receptor subtype 3, which demonstrates that it has a unique pharmacology compared with other mammalian bombesin receptors. J Biol Chem, 272 (41): 26062-71. [PMID:9325344]

13. Matsufuji T, Shimada K, Kobayashi S, Ichikawa M, Kawamura A, Fujimoto T, Arita T, Hara T, Konishi M, Abe-Ohya R et al.. (2015) Synthesis and biological evaluation of novel chiral diazepine derivatives as bombesin receptor subtype-3 (BRS-3) agonists incorporating an antedrug approach. Bioorg Med Chem, 23 (1): 89-104. [PMID:25497965]

14. Matsufuji T, Shimada K, Kobayashi S, Kawamura A, Fujimoto T, Arita T, Hara T, Konishi M, Abe-Ohya R, Izumi M et al.. (2014) Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration. Bioorg Med Chem Lett, 24 (3): 750-5. [PMID:24412111]

15. Moody TW, Mantey SA, Moreno P, Nakamura T, Lacivita E, Leopoldo M, Jensen RT. (2015) ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth. Peptides, 64: 55-61. [PMID:25554218]

16. Moreno P, Mantey SA, Nuche-Berenguer B, Reitman ML, Gonzalez N, , Coy DH, Jensen RT. (2013) Comparative Pharmacology of Bombesin Receptor Subtype-3, Nonpeptide Agonist MK-5046, a Universal Peptide Agonist, and Peptide Antagonist Bantag-1 for Human Bombesin Receptors. Pharmacol Exp Therap, 347 (1): 100-116. [PMID:23892571]

17. Pringle KG, Tadros MA, Callister RJ, Lumbers ER. (2011) The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: roles in trophoblast invasion and angiogenesis?. Placenta, 32 (12): 956-62. [PMID:22018415]

18. Ramos-Alvarez I, Iordanskaia T, Mantey SA, Jensen RT. (2022) The Nonpeptide Agonist MK-5046 Functions As an Allosteric Agonist for the Bombesin Receptor Subtype-3. J Pharmacol Exp Ther, 382 (2): 66-78. [PMID:35644465]

19. Ramos-Alvarez I, Lee L, Mantey SA, Jensen RT. (2019) Development and Characterization of a Novel, High-Affinity, Specific, Radiolabeled Ligand for BRS-3 Receptors. J Pharmacol Exp Ther, 369 (3): 454-465. [PMID:30971479]

20. Ramos-Álvarez I, Nakamura T, Mantey SA, Moreno P, Nuche-Berenguer B, Jensen RT. (2016) Novel chiral-diazepines function as specific, selective receptor agonists with variable coupling and species variability in human, mouse and rat BRS-3 receptor cells. Peptides, 75: 8-17. [PMID:26524625]

21. Sebhat IK, Franklin C, Lo MM, Chen D, Jewell JP, Miller R, Pang J, Palyha O, Kan Y, Kelly TM et al.. (2011) Discovery of MK-5046, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity. ACS Med Chem Lett, 2 (1): 43-7. [PMID:24900253]

22. Wu L, Cui J, Zhao C, Wang Z, Lu J, Li S, Jia J, Xiao H, Zhang Y. (2023) Discovery of Dimethyl Shikonin Oxime 5a, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Type 2 Diabetes Mellitus. J Med Chem, 66 (12): 8011-8029. [PMID:37272653]

23. Zhu Y, Wu L, Zhao Y, Wang Z, Lu J, Yu Y, Xiao H, Zhang Y. (2022) Discovery of oridonin as a novel agonist for BRS-3. Phytomedicine, 100: 154085. [PMID:35405616]

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.

Mas1, BB3/Brs3, GPR17 C

Overview

Receptors

References

How to cite this family page

Mas1, BB₃/Brs3, GPR17 C