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Distinct Dopamine D2 Receptor Antagonists Differentially Impact D2 Receptor Oligomerization

التفاصيل البيبلوغرافية
العنوان: Distinct Dopamine D2 Receptor Antagonists Differentially Impact D2 Receptor Oligomerization
المؤلفون: Elise Wouters, Adrián Ricarte Marín, James Andrew Rupert Dalton, Jesús Giraldo, Christophe Stove
المصدر: International Journal of Molecular Sciences, Vol 20, Iss 7, p 1686 (2019)
بيانات النشر: MDPI AG, 2019.
سنة النشر: 2019
المجموعة: LCC:Biology (General)
LCC:Chemistry
مصطلحات موضوعية: G protein-coupled receptor (GPCR), dimerization, oligomerization, protein complementation assay, NanoLuc binary technology (NanoBiT), dopamine D2 receptor, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Dopamine D2 receptors (D2R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of schizophrenia. Pharmacological targeting and modulation of the equilibrium of these receptor homodimers might lead to a better understanding of the critical role played by these complexes in physiological and pathological conditions. Whereas agonist addition has shown to prolong the D2R dimer lifetime and increase the level of dimer formation, the possible influence of D2R antagonists on dimerization has remained rather unexplored. Here, using a live-cell reporter assay based on the functional complementation of a split Nanoluciferase, a panel of six D2R antagonists were screened for their ability to modulate the level of D2LR dimer formation. Incubation with the D2R antagonist spiperone decreased the level of D2LR dimer formation significantly by 40–60% in real-time and after long-term (≥16 h) incubations. The fact that dimer formation of the well-studied A2a–D2LR dimer was not altered following incubation with spiperone supports the specificity of this observation. Other D2R antagonists, such as clozapine, risperidone, and droperidol did not significantly evoke this dissociation event. Furthermore, molecular modeling reveals that spiperone presents specific Tyr1995.48 and Phe3906.52 conformations, compared to clozapine, which may determine D2R homodimerization.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1422-0067
Relation: https://www.mdpi.com/1422-0067/20/7/1686; https://doaj.org/toc/1422-0067
DOI: 10.3390/ijms20071686
URL الوصول: https://doaj.org/article/3c4507ccf034456caed5af23750ddc7b
رقم الأكسشن: edsdoj.3c4507ccf034456caed5af23750ddc7b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14220067
DOI:10.3390/ijms20071686