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. 2022 Jul 8;3(4):zqac033. doi: 10.1093/function/zqac033

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© The Author(s) 2022. Published by Oxford University Press on behalf of American Physiological Society.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Graphical Abstract — Store-Operated Calcium Entry is mediated by receptor (R) stimulation, transduced by tyrosine kinases (TK) or G proteins (G), leading to activation of phospholipase C and inositol 1,4,5 trisphosphate (IP3) production. The opening of IP3 receptors (IP3R) in the endoplasmic reticulum (ER) results in store depletion that is sensed by STIM1/2, which activate calcium (Ca2+) influx via Calcium Release-Activated Calcium (CRAC) channels. Several cannabinoids (CBx) inhibit these CRAC channels and thereby suppress signal transduction through the Calmodulin (CaM) - Calcineurin (CaN) - Nuclear Factor of Activated T cells (NFAT) pathway, which regulates cytokine release and cell proliferation.