Noncanonical Potentiation of Evoked Quantal Release of Acetylcholine by Cannabinoids Anandamide and 2-Arachidonoylglycerol in Mouse Motor Synapses

Tarasova, E. O.; Хоткина, Н. А.; Bogacheva, P. O.; Chernyshev, K. A.; Gaydukov, A. E.; Балезина, О. П.

doi:10.1134/s199074782106012x

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…In addition, 2-AG (1 µM) was also found to increase mEPP amplitude and QC, but not their frequency. Remarkably, these 2-AG effects were abolished only in the presence of PKA inhibitors, revealing that the mechanism by which the two endocannabinoids control mEPP is different [ 89 ]. In a previous study, Newman et al discovered that 2-AG mediates the muscarine M3 receptor-dependent inhibition of ACh release from nerve terminals through the same “retrograde mechanism” that occurs in the CNS.…”

Section: Myasthenia Gravismentioning

confidence: 99%

Cannabinoids, Endocannabinoids, and Synthetic Cannabimimetic Molecules in Neuromuscular Disorders

Iannotti

2023

IJMS

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Neuromuscular disorders (NMDs) encompass a large heterogeneous group of hereditary and acquired diseases primarily affecting motor neurons, peripheral nerves, and the skeletal muscle system. The symptoms of NMDs may vary depending on the specific condition, but some of the most common ones include muscle weakness, pain, paresthesias, and hyporeflexia, as well as difficulties with swallowing and breathing. NMDs are currently untreatable. Therapeutic options include symptomatic and experimental medications aimed at delaying and alleviating symptoms, in some cases supplemented by surgical and physical interventions. To address this unmet medical need, ongoing research is being conducted on new treatments, including studies on medical cannabis, endocannabinoids, and related molecules with cannabimimetic properties. In this context, a significant amount of knowledge about the safety and effectiveness of cannabinoids in NMDs has been obtained from studies involving patients with multiple sclerosis experiencing pain and spasticity. In recent decades, numerous other preclinical and clinical studies have been conducted to determine the potential benefits of cannabinoids in NMDs. This review article aims to summarize and provide an unbiased point of view on the current knowledge about the use of cannabinoids, endocannabinoids, and synthetic analogs in NMDs, drawing from an array of compelling studies.

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Section: Myasthenia Gravismentioning

confidence: 99%

Cannabinoids, Endocannabinoids, and Synthetic Cannabimimetic Molecules in Neuromuscular Disorders

Iannotti

2023

IJMS

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“…Neurophysiological research in the last few decades has provided evidence that changes in neurotransmitter quantal secretion in central synapses as well as in peripheral neuromuscular junctions may be due to variations in the number of simultaneously released quanta in response to nerve stimulation (i.e., quantal content) or to variations of the size of individual quanta (Morsch et al., 2018; Ruiz et al., 2011; Sulzer & Pothos, 2000; Tarasova, Khotkina, Bogacheva, et al., 2021; Westerink, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we have found that in mouse neuromuscular synapses, the endocannabinoid (EC) 2‐arachidonylglycerol (2‐AG) is able to increase the amplitude of miniature endplate potentials (MEPPs) by acting on presynaptic cannabinoid CB1‐type receptors. This increase was prevented by vesamicol, an inhibitor of acetylcholine (ACh) uptake into synaptic vesicles (Tarasova, Khotkina, Bogacheva, et al., 2021; Tarasova, Khotkina, Gaydukov, et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

Quantal size increase induced by the endocannabinoid 2‐arachidonoylglycerol requires activation of CGRP receptors in mouse motor synapses

Tarasova,

Bogacheva,

Chernyshev

et al. 2023

Synapse

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In mouse motor synapses, the exogenous application of the endocannabinoid (EC) 2‐arachidonoylglycerol (2‐AG) increases acetylcholine (ACh) quantal size due to the activation of CB1 receptors and the stimulation of ACh vesicular uptake. In the present study, microelectrode recordings of miniature endplate potentials (MEPP) revealed that this effect of 2‐AG is independent of brain‐derived neurotrophic factor (BDNF) signaling but involves the activation of calcitonin gene–related peptide (CGRP) receptors along with CB1 receptors. Potentiation of MEPP amplitude in the presence of 2‐AG was prevented by blockers of CGRP receptors and ryanodine receptors (RyR) and by inhibitors of phospholipase C (PLC) and Ca2+/calmodulin‐dependent protein kinase II (CaMKII). Therefore, we suggest a hypothetical chain of events, which starts from the activation of presynaptic CB1 receptors, involves PLC, RyR, and CaMKII, and results in CGRP release with the subsequent activation of presynaptic CGRP receptors. Activation of CGRP receptors is probably a part of a complex molecular cascade leading to the 2‐AG‐induced increase in ACh quantal size and MEPP amplitude. We propose that the same chain of events may also take place if 2‐AG is endogenously produced in mouse motor synapses, because the increase in MEPP amplitude that follows after prolonged tetanic muscle contractions (30 Hz, 2 min) was prevented by the blocking of CB1 receptors. This work may help to unveil the previously unknown aspects of the functional interaction between ECs and peptide modulators aimed at the regulation of quantal size and synaptic transmission.

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BDNF Prodomain Inhibits Neurotransmitter Quantal Release in Mouse Motor Synapses with the Necessary Participation of Sortilin and Adenosine A1-Receptors

Molchanova,

Balezina,

Gaydukov

2024

J Evol Biochem Phys

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Noncanonical Potentiation of Evoked Quantal Release of Acetylcholine by Cannabinoids Anandamide and 2-Arachidonoylglycerol in Mouse Motor Synapses

Cited by 6 publications

References 48 publications

Cannabinoids, Endocannabinoids, and Synthetic Cannabimimetic Molecules in Neuromuscular Disorders

Cannabinoids, Endocannabinoids, and Synthetic Cannabimimetic Molecules in Neuromuscular Disorders

Quantal size increase induced by the endocannabinoid 2‐arachidonoylglycerol requires activation of CGRP receptors in mouse motor synapses

BDNF Prodomain Inhibits Neurotransmitter Quantal Release in Mouse Motor Synapses with the Necessary Participation of Sortilin and Adenosine A1-Receptors

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