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Biomolecules
2020 Feb 12;102:. doi: 10.3390/biom10020283.
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Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System.
Akimov MG
,
Kudryavtsev DS
,
Kryukova EV
,
Fomina-Ageeva EV
,
Zakharov SS
,
Gretskaya NM
,
Zinchenko GN
,
Serkov IV
,
Makhaeva GF
,
Boltneva NP
,
Kovaleva NV
,
Serebryakova OG
,
Lushchekina SV
,
Palikov VA
,
Palikova Y
,
Dyachenko IA
,
Kasheverov IE
,
Tsetlin VI
,
Bezuglov VV
.
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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.
RSF grant 18-74-10088 Russian Science Foundation, RSF grant 16-14-00215 p Russian Science Foundation, Project #0101-2019-0031 Ministry of Education and Science of the Russian Federation
Bezuglov,
[Arachidonoylcholine and N,N-dimethylaminoethyl arachidonate are new cholinergic compounds].
2001, Pubmed
Bezuglov,
[Arachidonoylcholine and N,N-dimethylaminoethyl arachidonate are new cholinergic compounds].
2001,
Pubmed
Bisogno,
N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo.
2000,
Pubmed
Brams,
A structural and mutagenic blueprint for molecular recognition of strychnine and d-tubocurarine by different cys-loop receptors.
2011,
Pubmed
Campoy,
Cholinergic system and cell proliferation.
2016,
Pubmed
Cheung,
Structures of human acetylcholinesterase in complex with pharmacologically important ligands.
2012,
Pubmed
Clementi,
Neuronal nicotinic receptors, important new players in brain function.
2000,
Pubmed
ELLMAN,
A new and rapid colorimetric determination of acetylcholinesterase activity.
1961,
Pubmed
Egleton,
Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis.
2008,
Pubmed
Harrison,
Muscarinic signalling affects intracellular calcium concentration during the first cell cycle of sea urchin embryos.
2002,
Pubmed
Ivonnet,
Nicotinic acetylcholine receptors of the neuronal type occur in the plasma membrane of sea urchin eggs.
1997,
Pubmed
Kruse,
Muscarinic acetylcholine receptors: novel opportunities for drug development.
2014,
Pubmed
Kudryavtsev,
Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors.
2015,
Pubmed
,
Xenbase
Leung,
Serum metabolomic profiling and its association with 25-hydroxyvitamin D.
2020,
Pubmed
Makhaeva,
Conjugates of tacrine and 1,2,4-thiadiazole derivatives as new potential multifunctional agents for Alzheimer's disease treatment: Synthesis, quantum-chemical characterization, molecular docking, and biological evaluation.
2020,
Pubmed
Makhaeva,
Overview of novel multifunctional agents based on conjugates of γ-carbolines, carbazoles, tetrahydrocarbazoles, phenothiazines, and aminoadamantanes for treatment of Alzheimer's disease.
2019,
Pubmed
Makhaeva,
Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors.
2016,
Pubmed
Masson,
Effects of viscosity and osmotic stress on the reaction of human butyrylcholinesterase with cresyl saligenin phosphate, a toxicant related to aerotoxic syndrome: kinetic and molecular dynamics studies.
2013,
Pubmed
Moreno,
Epithelial propionyl- and butyrylcholine as novel regulators of colonic ion transport.
2016,
Pubmed
Morris,
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.
2009,
Pubmed
Mucchietto,
α9- and α7-containing receptors mediate the pro-proliferative effects of nicotine in the A549 adenocarcinoma cell line.
2018,
Pubmed
Nicolet,
Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products.
2003,
Pubmed
Peng,
Chronic nicotine treatment up-regulates alpha3 and alpha7 acetylcholine receptor subtypes expressed by the human neuroblastoma cell line SH-SY5Y.
1997,
Pubmed
Rossier,
Acetyl-coenzyme A and coenzyme A analogues. Their effects on rat brain choline acetyltransferase.
1977,
Pubmed
Rucktooa,
Insight in nAChR subtype selectivity from AChBP crystal structures.
2009,
Pubmed
Shelukhina,
Azemiopsin, a Selective Peptide Antagonist of Muscle Nicotinic Acetylcholine Receptor: Preclinical Evaluation as a Local Muscle Relaxant.
2018,
Pubmed
,
Xenbase
Smit,
A glia-derived acetylcholine-binding protein that modulates synaptic transmission.
2001,
Pubmed
Tripathy,
A single molecular distance predicts agonist binding energy in nicotinic receptors.
2019,
Pubmed
Utkin,
Azemiopsin from Azemiops feae viper venom, a novel polypeptide ligand of nicotinic acetylcholine receptor.
2012,
Pubmed
,
Xenbase
Vorkas,
Untargeted UPLC-MS profiling pipeline to expand tissue metabolome coverage: application to cardiovascular disease.
2015,
Pubmed
Vorkas,
Metabolic phenotyping of atherosclerotic plaques reveals latent associations between free cholesterol and ceramide metabolism in atherogenesis.
2015,
Pubmed
Wang,
α7 nicotinic acetylcholine receptors in lung cancer.
2018,
Pubmed
Wessler,
Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans.
2008,
Pubmed
Yan,
Recombinant Newcastle disease virus rL-RVG enhances the apoptosis and inhibits the migration of A549 lung adenocarcinoma cells via regulating alpha 7 nicotinic acetylcholine receptors in vitro.
2017,
Pubmed
Zakrzewicz,
Canonical and Novel Non-Canonical Cholinergic Agonists Inhibit ATP-Induced Release of Monocytic Interleukin-1β via Different Combinations of Nicotinic Acetylcholine Receptor Subunits α7, α9 and α10.
2017,
Pubmed
Zarei,
Modulation of plasma and urine metabolome in colorectal cancer survivors consuming rice bran.
2019,
Pubmed
Zeleznik,
Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.
2018,
Pubmed
Zhao,
Blocking M2 muscarinic receptor signaling inhibits tumor growth and reverses epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC).
2015,
Pubmed
van de Loosdrecht,
A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia.
1994,
Pubmed