Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65172610.31857/S0869813924100013VSFVPEArticlesСтатьиReview ArticleThe role of dopamine receptor dimer complexes in the pathogenesis of depressionРоль димерных комплексов дофаминовых рецепторов в патогенезе депрессииGerasimovА. А.ГерасимовА. А.
Russian Federation
drewgerasimov@gmail.comSmirnovaО. V.СмирноваО. В.
Russian Federation
drewgerasimov@gmail.comLomonosov Moscow State UniversityМосковский государственный университет имени М. В. Ломоносова15102024110101541155802022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/651726

This abstract discusses the oligomerization of G protein-coupled receptors (GPCRs), which significantly expands the functional capabilities of cells in living organisms by modulating intracellular signaling pathways. This provides a variety of physiological effects in both normal and pathological states. The structure and localization in the brain of one of the most studied heterodimers, the D1-D2 receptor complex, and its signaling cascades, which correlate with the development of depressive disorders, are examined. Sexual differences in the functioning of this heterodimer are analyzed, and the issue of the selectivity of bivalent synthetic ligands in activating specific intracellular pathways is discussed, highlighting their potential as therapeutic targets for the targeted treatment of depressive disorders. The concluding part of the abstract addresses the diversity of dopamine receptor heterodimers with other members of the GPCR family and their role in the pathophysiology of depression.

В настоящем обзоре обсуждается олигомеризация рецепторов, сопряженных с G-белком (GPCRs), позволяющая существенно расширить спектр функциональных возможностей клеток живых организмов путем модулирования внутриклеточных каскадов. Это обеспечивает разнообразие физиологических эффектов как в норме, так и при патологии. Рассмотрена структура и локализация в головном мозге одного из наиболее изученных гетеродимеров, комплекса D1-D2-рецепторов, и его сигнальные каскады, коррелирующие с развитием депрессивных расстройств. Проанализированы половые различия в функционировании данного гетеродимера, обсуждается вопрос о селективности бивалентных синтетических лигандов в отношении запуска определенных внутриклеточных каскадов, что делает их перспективной терапевтической мишенью для адресной терапии депрессивных расстройств. Заключительная часть обзора посвящена разнообразию гетеродимеров дофаминовых рецепторов с другими представителями семейства GPCR и их месту в патофизиологии депрессии.

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