Drug discovery opportunities at the endothelin B receptor-related orphan g protein-coupled receptors, GPR37 and GPR37L1

Frontiers in Pharmacology

Volumn 6, Issue NOV, 2015, Pages

  Smith, Nicola J ^a,b  

^a VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Endothelin; ETB; G protein coupled receptor; GPR37; GPR37L1; Orphan; Pael R; Parkin

Indexed keywords

BOMBESIN RECEPTOR; DOPAMINE TRANSPORTER; ENDOTHELIN 1; ENDOTHELIN 2; ENDOTHELIN 3; ENDOTHELIN A RECEPTOR; ENDOTHELIN B RECEPTOR; ENDOTHELIN RECEPTOR ANTAGONIST; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 37; G PROTEIN COUPLED RECEPTOR 37L1; PARKIN; UBIQUITIN; UNCLASSIFIED DRUG;

AUTISM; BINDING AFFINITY; BIPOLAR DISORDER; BRAIN DEVELOPMENT; CARBOXY TERMINAL SEQUENCE; CHROMATIN IMMUNOPRECIPITATION; CYTOTOXICITY; ENDOPLASMIC RETICULUM STRESS; ENDOTHELIUM; EXPRESSED SEQUENCE TAG; GENETIC TRANSCRIPTION; GLYCOSYLATION; HUMAN; HYDROPHOBICITY; IMMUNOREACTIVITY; MAJOR DEPRESSION; MOLECULAR CLONING; MOLECULAR DYNAMICS; NEUROTOXICITY; NONHUMAN; OPEN FIELD TEST; PALMITOYLATION; PARKINSON DISEASE; PARKINSONISM; PATHOGENESIS; PHYLOGENETIC TREE; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN PURIFICATION; PROTEIN TARGETING; PULMONARY HYPERTENSION; REVIEW; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY; TESTIS DEVELOPMENT; UNFOLDED PROTEIN RESPONSE; UPREGULATION;

EID: 84949787365     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2015.00275     Document Type: Review

References (79)

1. Alexander, S. P., Benson, H. E., Faccenda, E., Pawson, A. J., Sharman, J. L., Spedding, M., et al. (2013). The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors. Br. J. Pharmacol. 170, 1459-1581. doi: 10.1111/bph.12445
2. Arai, H., Hori, S., Aramori, I., Ohkubo, H., and Nakanishi, S. (1990). Cloning and expression of a cDNA encoding an endothelin receptor. Nature 348, 730-732. doi: 10.1038/348730a0
3. Arking, D. E., Reinier, K., Post, W., Jui, J., Hilton, G., O'Connor, A., et al. (2010). Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. PLoS ONE 5:e9879. doi: 10.1371/journal.pone.0009879
4. Bakkaloglu, B., O'Roak, B. J., Louvi, A., Gupta, A. R., Abelson, J. F., Morgan, T. M., et al. (2008). Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am. J. Hum. Genet. 82, 165-173. doi: 10.1016/j.ajhg.2007.09.017
5. Bodenmuller, H., and Schaller, H. C. (1981). Conserved amino acid sequence of a neuropeptide, the head activator, from coelenterates to humans. Nature 293, 579-580. doi: 10.1038/293579a0
6. Campana, W. M., Hiraiwa, M., and O'Brien, J. S. (1998). Prosaptide activates the MAPK pathway by a G-protein-dependent mechanism essential for enhanced sulfatide synthesis by Schwann cells. FASEB J. 12, 307-314.
7. Chaudhuri, K. R., Healy, D. G., Schapira, A. H., and National Institute for Clinical, E. (2006). Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 5, 235-245. doi: 10.1016/S1474-4422(06)70373-8
8. Chung, K. K., Dawson, V. L., and Dawson, T. M. (2001). The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders. Trends Neurosci. 24, S7-S14. doi: 10.1016/S0166-2236(01)00003-0
9. Cruceanu, C., Tan, P. P., Rogic, S., Lopez, J. P., Torres-Platas, S. G., Gigek, C. O., et al. (2015). Transcriptome sequencing of the anterior cingulate in bipolar disorder: dysregulation of G protein-coupled receptors. Am. J. Psychiatry doi: 10.1176/appi.ajp.2015.14101279 [Epub ahead of print].
10. Davenport, A. P., Alexander, S. P., Sharman, J. L., Pawson, A. J., Benson, H. E., Monaghan, A. E., 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, 967-986. doi: 10.1124/pr.112.007179
11. Donohue, P. J., Shapira, H., Mantey, S. A., Hampton, L. L., Jensen, R. T., and Battey, J. F. (1998). A human gene encodes a putative G protein-coupled receptor highly expressed in the central nervous system. Brain Res. Mol. Brain Res. 54, 152-160. doi: 10.1016/S0169-328X(97)00336-7
12. Dunham, J. H., and Hall, R. A. (2009). Enhancement of the surface expression of G protein-coupled receptors. Trends Biotechnol. 27, 541-545. doi: 10.1016/j.tibtech.2009.06.005
13. Dunham, J. H., Meyer, R. C., Garcia, E. L., and Hall, R. A. (2009). GPR37 surface expression enhancement via N-terminal truncation or protein-protein interactions. Biochemistry 48, 10286-10297. doi: 10.1021/bi9013775
14. Dutta, P., O'Connell, K. E., Ozkan, S. B., Sailer, A. W., and Dev, K. K. (2014). The protein interacting with C-kinase (PICK1) interacts with and attenuates parkin-associated endothelial-like (PAEL) receptor-mediated cell death. J. Neurochem. 130, 360-373. doi: 10.1111/jnc.12741
15. Fredriksson, R., Lagerström, M. C., Lundin, L. G., and Schiöth, H. B. (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256-1272. doi: 10.1124/mol.63.6.1256
16. Fujita-Jimbo, E., Yu, Z. L., Li, H., Yamagata, T., Mori, M., Momoi, T., et al. (2012). Mutation in Parkinson disease-associated, G-protein-coupled receptor 37 (GPR37/PaelR) is related to autism spectrum disorder. PLoS ONE 7:e51155. doi: 10.1371/journal.pone.0051155
17. Gandia, J., Fernandez-Duenas, V., Morato, X., Caltabiano, G., Gonzalez-Muniz, R., Pardo, L., et al. (2013). The Parkinson's disease-associated GPR37 receptor-mediated cytotoxicity is controlled by its intracellular cysteine-rich domain. J. Neurochem. 125, 362-372. doi: 10.1111/jnc.12196
18. Gandia, J., Morato, X., Stagljar, I., Fernandez-Duenas, V., and Ciruela, F. (2015). Adenosine A2A receptor-mediated control of pilocarpine-induced tremulous jaw movements is Parkinson's disease-associated GPR37 receptor-dependent. Behav. Brain Res. 288, 103-106. doi: 10.1016/j.bbr.2015.04.001
19. Goldberg, M. S., Fleming, S. M., Palacino, J. J., Cepeda, C., Lam, H. A., Bhatnagar, A., et al. (2003). Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J. Biol. Chem. 278, 43628-43635. doi: 10.1074/jbc. M308947200
20. Hallett, M. (2012). Parkinson's disease tremor: pathophysiology. Parkinsonism Relat. Disord. 18(Suppl. 1), S85-S86. doi: 10.1016/S1353-8020(11)70027-X
21. Hiraiwa, M., Campana, W. M., Martin, B. M., and O'Brien, J. S. (1997). Prosaposin receptor: evidence for a G-protein-associated receptor. Biochem. Biophys. Res. Commun. 240, 415-418. doi: 10.1006/bbrc.1997.7673
22. Imai, Y., Soda, M., Hatakeyama, S., Akagi, T., Hashikawa, T., Nakayama, K. I., et al. (2002). CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol. Cell 10, 55-67. doi: 10.1016/S1097-2765(02)00583-X
23. Imai, Y., Soda, M., Inoue, H., Hattori, N., Mizuno, Y., and Takahashi, R. (2001). An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105, 891-902. doi: 10.1016/S0092-8674(01)00407-X
24. Imai, Y., Soda, M., and Takahashi, R. (2000). Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 275, 35661-35664. doi: 10.1074/jbc. C000447200
25. Inoue, A., Yanagisawa, M., Kimura, S., Kasuya, Y., Miyauchi, T., Goto, K., et al. (1989). The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl. Acad. Sci. U.S.A. 86, 2863-2867. doi: 10.1073/pnas.86.8.2863
26. Itier, J. M., Ibanez, P., Mena, M. A., Abbas, N., Cohen-Salmon, C., Bohme, G. A., et al. (2003). Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum. Mol. Genet. 12, 2277-2291. doi: 10.1093/hmg/ddg239
27. Ito, J., Ito, M., Nambu, H., Fujikawa, T., Tanaka, K., Iwaasa, H., et al. (2009). Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice. Cell Tissue Res. 338, 257-269. doi: 10.1007/s00441-009-0859-x
28. Junaid, M. A., Kuizon, S., Cardona, J., Azher, T., Murakami, N., Pullarkat, R. K., et al. (2011). Folic acid supplementation dysregulates gene expression in lymphoblastoid cells-implications in nutrition. Biochem. Biophys. Res. Commun. 412, 688-692. doi: 10.1016/j.bbrc.2011.08.027
29. Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., et al. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608. doi: 10.1038/33416
30. Kitao, Y., Imai, Y., Ozawa, K., Kataoka, A., Ikeda, T., Soda, M., et al. (2007). Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum. Mol. Genet. 16, 50-60. doi: 10.1093/hmg/ddl439
31. Kohan, D. E., Rossi, N. F., Inscho, E. W., and Pollock, D. M. (2011). Regulation of blood pressure and salt homeostasis by endothelin. Physiol. Rev. 91, 1-77. doi: 10.1152/physrev.00060.2009
32. Kubota, K., Niinuma, Y., Kaneko, M., Okuma, Y., Sugai, M., Omura, T., et al. (2006). Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. J. Neurochem. 97, 1259-1268. doi: 10.1111/j.1471-4159.2006.03782.x
33. Lagerstrom, M. C., and Schioth, H. B. (2008). Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 7, 339-357. doi: 10.1038/nrd2518
34. La Sala, G., Marazziti, D., Di Pietro, C., Golini, E., Matteoni, R., and Tocchini-Valentini, G. P. (2015). Modulation of Dhh signaling and altered Sertoli cell function in mice lacking the GPR37-prosaposin receptor. FASEB J. 29, 2059-2069. doi: 10.1096/fj.14-269209
35. Leng, N., Gu, G., Simerly, R. B., and Spindel, E. R. (1999). Molecular cloning and characterization of two putative G protein-coupled receptors which are highly expressed in the central nervous system. Brain Res. Mol. Brain Res. 69, 73-83. doi: 10.1016/S0169-328X(99)00092-3
36. Li, Z. S., Schmauss, C., Cuenca, A., Ratcliffe, E., and Gershon, M. D. (2006). Physiological modulation of intestinal motility by enteric dopaminergic neurons and the D2 receptor: analysis of dopamine receptor expression, location, development, and function in wild-type and knock-out mice. J. Neurosci. 26, 2798-2807. doi: 10.1523/JNEUROSCI.4720-05.2006
37. Liu, F., Zhu, C., Huang, X., Cai, J., Wang, H., Wang, X., et al. (2014). A low level of GPR37 is associated with human hepatocellular carcinoma progression and poor patient survival. Pathol. Res. Pract. 210, 885-892. doi: 10.1016/j.prp.2014.07.011
38. Liu, J., Wang, C. Y., and O'Brien, J. S. (2001). Prosaptide D5, a retro-inverso 11-mer peptidomimetic, rescued dopaminergic neurons in a model of Parkinson's disease. FASEB J. 15, 1080-1082. doi: 10.1096/fj.00-0603fje
39. Lockhart, P. J., O'Farrell, C. A., and Farrer, M. J. (2004). It's a double knock-out! The quaking mouse is a spontaneous deletion of parkin and parkin co-regulated gene (PACRG). Mov. Disord. 19, 101-104. doi: 10.1002/mds.20000
40. Lopes, J. P., Morato, X., Souza, C., Pinhal, C., Machado, N. J., Canas, P. M., et al. (2015). The role of Parkinson's disease-associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system. J. Neurochem. 134, 135-146. doi: 10.1111/jnc.13109
41. Lundius, E. G., Stroth, N., Vukojevic, V., Terenius, L., and Svenningsson, P. (2013). Functional GPR37 trafficking protects against toxicity induced by 6-OHDA, MPP+ or rotenone in a catecholaminergic cell line. J. Neurochem. 124, 410-417. doi: 10.1111/jnc.12081
42. Lundius, E. G., Vukojevic, V., Hertz, E., Stroth, N., Cederlund, A., Hiraiwa, M., et al. (2014). GPR37 protein trafficking to the plasma membrane regulated by prosaposin and GM1 gangliosides promotes cell viability. J. Biol. Chem. 289, 4660-4673. doi: 10.1074/jbc. M113.510883
43. Maguire, J. J., and Davenport, A. P. (2014). Endothelin@25-new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12. Br. J. Pharmacol. 171, 5555-5572. doi: 10.1111/bph.12874
44. Mandillo, S., Golini, E., Marazziti, D., Di Pietro, C., Matteoni, R., and Tocchini-Valentini, G. P. (2013). Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect. Genes Brain Behav. 12, 465-477. doi: 10.1111/gbb.12041
45. Marazziti, D., Di Pietro, C., Golini, E., Mandillo, S., La Sala, G., Matteoni, R., et al. (2013). Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor. Proc. Natl. Acad. Sci. U.S.A. 110, 16486-16491. doi: 10.1073/pnas.1314819110
46. Marazziti, D., Di Pietro, C., Golini, E., Mandillo, S., Matteoni, R., and Tocchini-Valentini, G. P. (2009). Induction of macroautophagy by overexpression of the Parkinson's disease-associated GPR37 receptor. FASEB J. 23, 1978-1987. doi: 10.1096/fj.08-121210
47. Marazziti, D., Di Pietro, C., Mandillo, S., Golini, E., Matteoni, R., and Tocchini-Valentini, G. P. (2011). Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, ΔFosB expression, and conditioned place preference to amphetamine and cocaine. FASEB J. 25, 2071-2081. doi: 10.1096/fj.10-175737
48. Marazziti, D., Gallo, A., Golini, E., Matteoni, R., and Tocchini-Valentini, G. P. (1998). Molecular cloning and chromosomal localization of the mouse Gpr37 gene encoding an orphan G-protein-coupled peptide receptor expressed in brain and testis. Genomics 53, 315-324. doi: 10.1006/geno.1998.5433
49. Marazziti, D., Golini, E., Gallo, A., Lombardi, M. S., Matteoni, R., and Tocchini-Valentini, G. P. (1997). Cloning of GPR37, a gene located on chromosome 7 encoding a putative G-protein-coupled peptide receptor, from a human frontal brain EST library. Genomics 45, 68-77. doi: 10.1006/geno.1997.4900
50. Marazziti, D., Golini, E., Mandillo, S., Magrelli, A., Witke, W., Matteoni, R., et al. (2004). Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor. Proc. Natl. Acad. Sci. U.S.A. 101, 10189-10194. doi: 10.1073/pnas.0403661101
51. Marazziti, D., Mandillo, S., Di Pietro, C., Golini, E., Matteoni, R., and Tocchini-Valentini, G. P. (2007). GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. Proc. Natl. Acad. Sci. U.S.A. 104, 9846-9851. doi: 10.1073/pnas.0703368104
52. Mazzuca, M. Q., and Khalil, R. A. (2012). Vascular endothelin receptor type B: structure, function and dysregulation in vascular disease. Biochem. Pharmacol. 84, 147-162. doi: 10.1016/j.bcp.2012.03.020
53. Meyer, R. C., Giddens, M. M., Schaefer, S. A., and Hall, R. A. (2013). GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. Proc. Natl. Acad. Sci. U.S.A. 110, 9529-9534. doi: 10.1073/pnas.1219004110
54. Min, K. D., Asakura, M., Liao, Y., Nakamaru, K., Okazaki, H., Takahashi, T., et al. (2010). Identification of genes related to heart failure using global gene expression profiling of human failing myocardium. Biochem. Biophys. Res. Commun. 393, 55-60. doi: 10.1016/j.bbrc.2010.01.076
55. Misasi, R., Sorice, M., Garofalo, T., Griggi, T., Campana, W. M., Giammatteo, M., et al. (1998). Colocalization and complex formation between prosaposin and monosialoganglioside GM3 in neural cells. J. Neurochem. 71, 2313-2321. doi: 10.1046/j.1471-4159.1998.71062313.x
56. 35S]GTPγS binding as an index of total G-protein and Gα-subtype-specific activation by GPCRs. Methods Mol. Biol. 746, 263-275. doi: 10.1007/978-1-61779-126-0_14
57. Murakami, T., Shoji, M., Imai, Y., Inoue, H., Kawarabayashi, T., Matsubara, E., et al. (2004). Pael-R is accumulated in Lewy bodies of Parkinson's disease. Ann. Neurol. 55, 439-442. doi: 10.1002/ana.20064
58. Negre-Pages, L., Grandjean, H., Lapeyre-Mestre, M., Montastruc, J. L., Fourrier, A., Lepine, J. P., et al. (2010). Anxious and depressive symptoms in Parkinson's disease: the French cross-sectionnal DoPaMiP study. Mov. Disord. 25, 157-166. doi: 10.1002/mds.22760
59. Omura, T., Kaneko, M., Okuma, Y., Orba, Y., Nagashima, K., Takahashi, R., et al. (2006). A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin. J. Neurochem. 99, 1456-1469. doi: 10.1111/j.1471-4159.2006.04155.x
60. Rask-Andersen, M., Masuram, S., and Schioth, H. B. (2014). The druggable genome: evaluation of drug targets in clinical trials suggests major shifts in molecular class and indication. Annu. Rev. Pharmacol. Toxicol. 54, 9-26. doi: 10.1146/annurev-pharmtox-011613-135943
61. Rezgaoui, M., Susens, U., Ignatov, A., Gelderblom, M., Glassmeier, G., Franke, I., et al. (2006). The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37. J. Cell Sci. 119, 542-549. doi: 10.1242/jcs.02766
62. Rubin, L. J., Badesch, D. B., Barst, R. J., Galie, N., Black, C. M., Keogh, A., et al. (2002). Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. 346, 896-903. doi: 10.1056/NEJMoa012212
63. Sakurai, T., Yanagisawa, M., Takuwa, Y., Miyazaki, H., Kimura, S., Goto, K., et al. (1990). Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature 348, 732-735. doi: 10.1038/348732a0
64. Scott, B., Borgman, A., Engler, H., Johnels, B., and Aquilonius, S. M. (2000). Gender differences in Parkinson's disease symptom profile. Acta Neurol. Scand. 102, 37-43. doi: 10.1034/j.1600-0404.2000.102001037.x
65. Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., et al. (2000). Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25, 302-305. doi: 10.1038/77060
66. Smith, N. J., and Milligan, G. (2010). Allostery at G protein-coupled receptor homo-and heteromers: uncharted pharmacological landscapes. Pharmacol. Rev. 62, 701-725. doi: 10.1124/pr.110.002667
67. Smith, N. J., Ward, R. J., Stoddart, L. A., Hudson, B. D., Kostenis, E., Ulven, T., et al. (2011). Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator. Mol. Pharmacol. 80, 163-173. doi: 10.1124/mol.110.070789
68. Southern, C., Cook, J. M., Neetoo-Isseljee, Z., Taylor, D. L., Kettleborough, C. A., Merritt, A., et al. (2013). Screening β-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J. Biomol. Screen. 18, 599-609. doi: 10.1177/1087057113475480
69. Tanabe, Y., Fujita-Jimbo, E., Momoi, M. Y., and Momoi, T. (2015). CASPR2 forms a complex with GPR37 via MUPP1 but not with GPR37(R558Q), an autism spectrum disorder-related mutation. J. Neurochem. 134, 783-793. doi: 10.1111/jnc.13168
70. Tomita, H., Ziegler, M. E., Kim, H. B., Evans, S. J., Choudary, P. V., Li, J. Z., et al. (2013). G protein-linked signaling pathways in bipolar and major depressive disorders. Front. Genet. 4:297. doi: 10.3389/fgene.2013.00297
71. Toyota, M., Kopecky, K. J., Toyota, M. O., Jair, K. W., Willman, C. L., and Issa, J. P. (2001). Methylation profiling in acute myeloid leukemia. Blood 97, 2823-2829. doi: 10.1182/blood. V97.9.2823
72. Valdenaire, O., Giller, T., Breu, V., Ardati, A., Schweizer, A., and Richards, J. G. (1998). A new family of orphan G protein-coupled receptors predominantly expressed in the brain. FEBS Lett. 424, 193-196. doi: 10.1016/S0014-5793(98)00170-7
73. Walker, J. K., Gainetdinov, R. R., Mangel, A. W., Caron, M. G., and Shetzline, M. A. (2000). Mice lacking the dopamine transporter display altered regulation of distal colonic motility. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G311-G318.
74. Wang, H. Q., Imai, Y., Inoue, H., Kataoka, A., Iita, S., Nukina, N., et al. (2008). Pael-R transgenic mice crossed with parkin deficient mice displayed progressive and selective catecholaminergic neuronal loss. J. Neurochem. 107, 171-185. doi: 10.1111/j.1471-4159.2008.05607.x
75. Wei, C. J., Augusto, E., Gomes, C. A., Singer, P., Wang, Y., Boison, D., et al. (2014). Regulation of fear responses by striatal and extrastriatal adenosine A2A receptors in forebrain. Biol. Psychiatry 75, 855-863. doi: 10.1016/j.biopsych.2013.05.003
76. Yanagisawa, M., Inoue, A., Ishikawa, T., Kasuya, Y., Kimura, S., Kumagaye, S., et al. (1988). Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc. Natl. Acad. Sci. U.S.A. 85, 6964-6967. doi: 10.1073/pnas.85.18.6964
77. Yang, Y., Nishimura, I., Imai, Y., Takahashi, R., and Lu, B. (2003). Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37, 911-924. doi: 10.1016/S0896-6273(03)00143-0
78. Zeng, Z., Su, K., Kyaw, H., and Li, Y. (1997). A novel endothelin receptor type-B-like gene enriched in the brain. Biochem. Biophys. Res. Commun. 233, 559-567. doi: 10.1006/bbrc.1997.6408
79. Zhang, Y., Gao, J., Chung, K. K., Huang, H., Dawson, V. L., and Dawson, T. M. (2000). Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl. Acad. Sci. U.S.A. 97, 13354-13359. doi: 10.1073/pnas.240347797