Cannabidiol as a modulator of α7 nicotinic receptors

Chrestia, Juan Facundo; Esandi, María del Carmen; Bouzat, Cecilia

doi:10.1007/s00018-022-04600-y

Cited by 7 publications

(4 citation statements)

References 75 publications

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“…In various neuronal cells high calcium signaling through the homopentameric α7 nAChR directs actin associated cytoskeletal dynamics leading to observable changes synaptic growth and plasticity [ 25 , 41 ]. An analogous mechanism for α7 nAChR-calcium signaling to the cytoskeleton exists in non-neuronal cells including immune and epithelial cells [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

α7 nicotinic acetylcholine receptor interaction with G proteins in breast cancer cell proliferation, motility, and calcium signaling

Öz¹,

King²,

Yang³

et al. 2023

PLoS ONE

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Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect of α7 nAChR on cell proliferation was abolished by application of Gαi/o and Gαq protein blockers. Specifically, application of the Gαi/o inhibitor pertussis toxin was found to abolish choline-mediated cell proliferation and intracellular calcium transient response. These findings were corroborated by expression of a G protein binding dominant negative nAChR subunit (α7345-348A), which resulted in significantly attenuating calcium signaling and cellular proliferation in response to choline. Our study shows a new role for G protein signaling in the mechanism of α7 nAChR-associated breast cancer growth.

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Section: Discussionmentioning

confidence: 99%

α7 nicotinic acetylcholine receptor interaction with G proteins in breast cancer cell proliferation, motility, and calcium signaling

Öz¹,

King²,

Yang³

et al. 2023

PLoS ONE

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“…The homopentameric channel formed by α7 nAChR subunits is inhibited by CBD (IC50 ~11 µM), whereas other cannabinoids, including THC, produced inefficient results [66]. The inhibitory effect of CBD on the nAChR channel is complex and likely arises from the stabilization of resting or desensitized conformational states of the nAChR complex [67]. Thus, CBD acts as an antagonist for nAChR, although, to our knowledge, there have been no attempts to reverse the reduction of NK cell cytotoxicity caused by nAChR agonists using CBD.…”

Section: Ion Channels and Ca 2+ Signalingmentioning

confidence: 99%

Molecular Targets for Cannabinoids in Natural Killer Cells: Do They Modulate the Antitumor Activity?

Olivas-Aguirre,

Gutiérrez-Iñiguez,

Pottosin

et al. 2024

Receptors

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Recent research has emphasized the potential of natural and synthetic cannabinoids as anticancer agents. Yet it remains unclear whether and in which sense cannabinoids affect the anticancer activity of NK cells, an important branch of anticancer immunity. Similar uncertainty exists regarding NK cells-based immunotherapy. Here we presented an overview of multiple cannabinoid targets as canonical (mainly CB2) and non-canonical receptors, ion channels, transporters, and enzymes, expressed in NK cells, along with underlying molecular mechanisms. Through them, cannabinoids can affect viability, proliferation, migration, cytokine production, and the overall anticancer activity of NK cells. Respective holistic studies are limited, and, mostly, are phenomenological, not linking observed effects with certain molecular targets. Another problem of existing studies is the lack of standardisation, so that diverse cannabinoids at variable concentrations and ways of administration are applied, and often, instead of purified NK cells, the whole lymphocyte population is used. Therefore, there is an urgent need for more focused, systemic, and in-depth studies of the impact of the cannabinoid toolkit on NK cell function, to critically address the compatibility and potential synergies between NK activity and cannabinoid utilization in the realm of anticancer interventions.

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“…CBD can inhibit α7nAChR in a dose-dependent manner and induce reduction of acetylcholine-evoked currents amplitude in in vitro BOSC-23 cells and in ex vivo patch clamp assays using rat hippocampal slices, while Δ 9 -THC does not affect this channel. Therefore, CBD acts as a NAM in the closed and desensitized states of these channels [ 69 , 70 ].…”

Section: Molecular Targets Reported For Cannabidiolmentioning

confidence: 99%

The Polypharmacological Effects of Cannabidiol

et al. 2023

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Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ9-tetrahydrocannabinol (∆9-THC) does. In contrast to ∆9-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a rationalized integration of the mechanisms of action of CBD on molecular targets and pharmacological implications in animal models and human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer’s disease, and inflammatory diseases, are presented. We identify around 56 different molecular targets for CBD, including enzymes and ion channels/metabotropic receptors involved in neurologic conditions. Herein, we compiled the knowledge found in the scientific literature on the multiple mechanisms of actions of CBD. The in vitro and in vivo findings are essential for fully understanding the polypharmacological nature of this natural product.

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Cannabidiol as a modulator of α7 nicotinic receptors

Cited by 7 publications

References 75 publications

α7 nicotinic acetylcholine receptor interaction with G proteins in breast cancer cell proliferation, motility, and calcium signaling

α7 nicotinic acetylcholine receptor interaction with G proteins in breast cancer cell proliferation, motility, and calcium signaling

Molecular Targets for Cannabinoids in Natural Killer Cells: Do They Modulate the Antitumor Activity?

The Polypharmacological Effects of Cannabidiol

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