Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System

Akimov, M.G.; Kudryavtsev, D.S.; Kryukova, E.V.; Fomina-Ageeva, E.V.; Zakharov, S.S.; Gretskaya, N.M.; Zinchenko, G.N.; Serkov, I.V.; Makhaeva, G.F.; Boltneva, N.P.; Kovaleva, N.V.; Serebryakova, O.G.; Lushchekina, S.V.; Palikov, V.A.; Palikova, Y.; Dyachenko, I.A.; Kasheverov, I.E.; Tsetlin, V.I.; Bezuglov, V.V.

Авторы: Akimov Mikhail G., Kudryavtsev Denis S., Kryukova Elena V., Fomina-Ageeva Elena V., Zakharov Stanislav S., Gretskaya Natalia M., Zinchenko Galina N., Serkov Igor V., Makhaeva Galina F., Boltneva Natalia P., Kovaleva Nadezhda V., Serebryakova Olga G., Lushchekina Sofya V., Palikov Victor A., Palikova Yulia, Dyachenko Igor A., Kasheverov Igor E., Tsetlin Victor I., Bezuglov Vladimir V.
Журнал: Biomolecules
Том: 10
Номер: 2
Год издания: 2020
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 283
DOI: 10.3390/biom10020283
Аннотация: Cholines acylated with unsaturated fatty acids are a recently discovered family of endogenous lipids. However, the data on the biological activity of acylcholines remain very limited. We hypothesized that acylcholines containing residues of arachidonic (AA-CHOL), oleic (Ol-CHOL), linoleic (Ln-CHOL), and docosahexaenoic (DHA-CHOL) acids act as modulators of the acetylcholine signaling system. In the radioligand binding assay, acylcholines showed inhibition in the micromolar range of both α7 neuronal nAChR overexpressed in GH4C1 cells and muscle type nAChR from Torpedo californica, as well as Lymnaea stagnalis acetylcholine binding protein. Functional response was checked in two cell lines endogenously expressing α7 nAChR. In SH-SY5Y cells, these compounds did not induce Ca2+ rise, but inhibited the acetylcholine-evoked Ca2+ rise with IC50 9 to 12 μM. In the A549 lung cancer cells, where α7 nAChR activation stimulates proliferation, Ol-CHOL, Ln-CHOL, and AA-CHOL dose-dependently decreased cell viability by up to 45%. AA-CHOL inhibited human erythrocyte acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by a mixed type mechanism with Ki = 16.7 ± 1.5 μM and αKi = 51.4 ± 4.1 μM for AChE and Ki = 70.5 ± 6.3 μM and αKi = 214 ± 17 μM for BChE, being a weak substrate of the last enzyme only, agrees with molecular docking results. Thus, long-chain unsaturated acylcholines could be viewed as endogenous modulators of the acetylcholine signaling system.
Добавил в систему: Лущекина Софья Владимировна

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Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling Systemстатья