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

Autor: Akimov MG; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Kudryavtsev DS; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Kryukova EV; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Fomina-Ageeva EV; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Zakharov SS; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Gretskaya NM; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Zinchenko GN; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Serkov IV; Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia., Makhaeva GF; Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia., Boltneva NP; Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia., Kovaleva NV; Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia., Serebryakova OG; Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia., Lushchekina SV; Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia.; Department of electrophysics of organic materials and nanostructures, Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia., Palikov VA; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Palikova Y; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Dyachenko IA; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Kasheverov IE; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow 119991, Russia., Tsetlin VI; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Bezuglov VV; Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2020 Feb 12; Vol. 10 (2). Date of Electronic Publication: 2020 Feb 12.
DOI: 10.3390/biom10020283
Abstrakt: 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 Ca 2+ rise, but inhibited the acetylcholine-evoked Ca 2+ rise with IC 50 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 K i = 16.7 ± 1.5 μM and αK i = 51.4 ± 4.1 μM for AChE and K i = 70.5 ± 6.3 μM and αK i = 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.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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