中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (11): 1912-1914.doi: 10.4103/1673-5374.259610

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

G蛋白偶联受体37可作为纹状体中腺苷能传递的重要调节剂

  

  • 出版日期:2019-11-15 发布日期:2019-11-15

G protein-coupled receptor 37 (GPR37) emerges as an important modulator of adenosinergic transmission in the striatum

Xavier Morató 1, 2, Rodrigo A. Cunha 3, 4, Francisco Ciruela 1, 2   

  1. 1Unitat de Farmacologia, Departament Patologia i Terapeutica Experimental, Facultat de Medicina, Instituto de Investigacion Biomedica de Bellvitge (IDIBELL), Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain;
    2Institut de Neurociencies, Universitat de Barcelona, Barcelona, Spain;
    3Center for Neuroscience and Cell Biology (CNC)-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal;
    4Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  • Online:2019-11-15 Published:2019-11-15
  • Contact: Francisco Ciruela, fciruela@ub.edu.
  • Supported by:

    This work was supported by Fondo Europeo de Desarrollo Regional (FEDER)/Ministerio de Ciencia, Innovación y Universidades–Agencia Estatal de Investigación (SAF2017-87349-R) and Instituto de Salud Carlos III (ISCIII) (PIE14/00034), the Catalan government (2017 SGR 1604), Fundació la Marató de TV3 (Grant 20152031), Fonds Wetenschappelijk Onderzoek (FWO) (SBO-140028) to FC and Centro 2020 (projects CENTRO-01-0145-FEDER-000008:BrainHealth 2020 and CENTRO-01-0246-FED-ER-000010), and Fundação para a Ciência e a Tecnologia (FCT) (projects PTDC/NEU-NMC/4154/2014 and POCI-01-0145-FEDER-031274) to RAC.

摘要:

orcid: 0000-0003-0832-3739 (Francisco Ciruela)

Abstract:

G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein-coupled receptor, which suffers a defective parking ubiquitination in autosomal recessive Parkinson’s disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death. Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A 2A receptor (A 2A R) in the striatum. In addition, we also reported some functional consequences of this direct interaction, whereby GPR37 deletion enhanced striatal A 2A R cell surface expression with a concomitant increase in A 2A R agonist-mediated cAMP accumulation; accordingly, an enhancement of A 2A R agonist-induced catalepsy and antagonist-induced locomotor activity was observed upon GPR37 deletion. Overall, it has been hypothesized that GPR37 might hold a chaperone-like activity controlling A 2A R cell surface targeting and function. However, the precise physiological function of GPR37 still is unidentified. The current findings now provide additional evidence for the role of GPR37 as a repressor of A 2A R function. Thus, while chronic A 2A R antagonist treatment (i.e., SCH58261, 1 mg/kg per day, intraperitoneal administration, 10 days) of mice lacking GPR37 did not affect the striatum-dependent cued learning, it enhanced locomotor sensitization. Moreover, chronic A 2A R blockade boosted striatal long-term depression (LTD) in corticostriatal synapses of GPR37 -/- but not of wild type mice; this observation correlated well with the adenosinergic neurochemical modifications present in GPR37 -/- mice, namely an increased density of A 2A R and decreased levels of adenosine. Overall, GPR37 emerged as key contestant controlling A 2A R function particularly upon chronic A 2A R blockade, thus delineating A 2A R-dependent long-term plastic changes in corticostriatal synapses.