Next Article in Journal
Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists
Previous Article in Journal
Auxin-Abscisic Acid Interactions in Plant Growth and Development
Previous Article in Special Issue
Different Effects of Nicotine and N-Stearoyl-ethanolamine on Episodic Memory and Brain Mitochondria of α7 Nicotinic Acetylcholine Receptor Knockout Mice
Open AccessArticle

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

1
Department of molecular neuroimmune signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia
2
Department medicinal and biological chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russia
3
Department of electrophysics of organic materials and nanostructures, Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia
4
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow 119991, Russia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(2), 283; https://doi.org/10.3390/biom10020283 (registering DOI)
Received: 7 January 2020 / Revised: 7 February 2020 / Accepted: 11 February 2020 / Published: 12 February 2020
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.
Keywords: nAChR; arachidonoylcholine; oleoylcholine; acylcholines; acetylcholinesterase nAChR; arachidonoylcholine; oleoylcholine; acylcholines; acetylcholinesterase
MDPI and ACS Style

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. Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System. Biomolecules 2020, 10, 283.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop