Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector83810.54101/ACEN.2022.4.6ReviewsОбзорыReview ArticleThe structural patterns of the potentiation and the blockade of inhibitory cys-loop receptors through the transmembrane domainСтруктурные закономерности потенциации и блокады тормозных цис-петельных рецепторов через трансмембранный доменhttps://orcid.org/0000-0001-7024-7461RossokhinAlexey V.РоссохинАлексей Владимирович
Russian Federation

Cand. Sci. (Phys.-Math.), leading researcher, Laboratory of functional synaptology, Brain Institute

к.ф-м.н., в.н.с. лаб. функциональной синаптологии Института мозга

alrossokhin@yandex.ruResearch Center of NeurolgyФГБНУ «Научный центр неврологии»2312202216444533003202220052022Copyright ©; 2022, Rossokhin A.V.Copyright ©; 2022, Россохин А.В.2022Rossokhin A.V.Россохин А.В.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/838

Anion-conducting cys-loop receptors activated by γ-aminobutyric acid (GABAАRs) and glycine (GlyRs) have inhibitory activity in the brain and spinal cord. GABAАRs and GlyRs are targets for various substances that potentiate or inhibit the receptor functions. Many of these substances are clinically significant agents to treat neurological and psychiatric conditions.

The review covers both our results and literature data on electrophysiology, mutations, and biochemistry of non-competitive antagonists, general anesthetics, barbiturates, and fenamates modulating GABAАRs and GlyRs. We focused on our own molecular modeling to determine the sites and the characteristics of binding of these substances to the GABAАR and GlyR transmembrane domain. With the structural patterns of the binding, we have identified possible molecular mechanisms of action for these substances.

Анион-проводящие цис-петельные рецепторы, активируемые γ-аминомасляной кислотой и глицином (ГАМКАР и ГлиР), ответственны за процессы торможения в головном и спинном мозге. Эти рецепторы являются мишенью для различных групп веществ, которые потенцируют или угнетают их функции. Многие из этих агентов являются клинически важными препаратами, используемыми для лечения неврологических и психических заболеваний.

В обзоре представлены как собственные, так и литературные данные по электрофизиологическим, мутационным и биохимическим исследованиям, которые изучают как вещества, относящиеся к классам неконкурентных антагонистов, общих анестетиков, барбитуратов и фенаматов, модулируют ГАМКАР и ГлиР. Большое внимание уделено собственным исследованиям с использованием методов молекулярного моделирования, которые позволили определить места и раскрыть основные характеристики связывания этих веществ с трансмембранным доменом ГАМКАР и ГлиР. Изучение структурных закономерностей связывания позволило нам выявить возможные молекулярные механизмы действия этих веществ.

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