Endocannabinoid system: structure, localization of cannabinoid receptors and their mechanism of action


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Abstract

Nowadays multiple effects from intake of active substance of the plant Cannabis sativa, Δ9-tetrahydrocannabinol (Δ9-THC), are of great interest to the scientists. It is proved that in the human body there is an endocannabinoid system, represented mainly by endogenous analogues of Δ9-THC and specific receptors, which can potentially become the objects of targeted therapy of many pathologies.

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INTRODUCTION Nowadays multiple effects from intake of active substance of the plant Cannabis sativa, Δ9-tetrahydrocannabinol (Δ9-THC), are of great interest to the scientists. It is proved that in the human body there is an endocannabinoid system, represented mainly by endogenous analogues of Δ9-THC and specific receptors, which can potentially become the objects of targeted therapy of many pathologies. PURPOSE The objective is to explain mechanism of endocannabinoid receptors’ action according to the modern scientific data. METHODS Analysis of articles from international databases Medline (PubMed), Web of Science, Scopus (2014-2019) was used. RESULTS Analysis of articles revealed that according to modern concepts, the endocannabinoid system is represented by two main types of receptors, CB1R and CB2R. Most of the effects of stimulation by Δ9-THC belong to CB1R, which is localized on the presynaptic membranes of neurons in brain, in liver, skeletal muscles, and pancreatic islets, thus taking a direct part in metabolism [1]. Depending on its localization this G protein-coupled receptor (GPCR) can both activate and inhibit adenylate cyclase, leading to significant changes in the concentration of cytoplasmic Ca2+. As a result, it is possible to reduce synaptic transmission by inhibiting the exocytosis of vesicles with neurotransmitters. Particularly, neurotoxicity is prevented by this mechanism. The CB2R receptor is predominantly expressed in testis, spleen, and at lower levels in brain reward regions. It is a Gi/o protein-coupled receptor that inhibits adenylate cyclase [2]. In addition to these receptors, there is a huge number of other receptors that play a less important role in our body, for example TRPV1 (transient receptor potential cation channel subfamily member 1), which is an ionotropic receptor, and GPR55 that also belongs to the GPCR receptor family [3]. CONCLUSION The effects of endocannabinoid system are realized through several types of receptors. The most common are CB1R and CB2R. The structure, localization of receptors and the effects of their stimulation suggest that knowing the receptor "map" of endocannabinoid system in our body with all the effects of their stimulation will make a significant breakthrough in the field of pharmacotherapy of many pathologies such as obesity, epilepsy, neurodegeneration, immunodeficiency, etc.
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About the authors

R K Movsisyan

I.M. Sechenov First Moscow State Medical University

T V Ivanova

I.M. Sechenov First Moscow State Medical University

E A Dyagileva

I.M. Sechenov First Moscow State Medical University

Y V Bulgakova

I.M. Sechenov First Moscow State Medical University

Candidate of Medical Sciences, Associate Professor at the Department of Normal Physiology

References

  1. Zou S., Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int. J. Mol. Sci. 2018;19:833.
  2. Estefanía M., Milena C., Ana K., Vicent C., and Enric C., The Endocannabinoid System as a Target in Cancer Diseases: Are We There Yet? Front Pharmacol. 2019; 10: 339. doi: 10.3389/fphar.2019.00339
  3. Ruth R. Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol. 2003 Nov; 140(5): 790-801. doi: 10.1038/sj.bjp.0705467

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