Editing Cannabinoid receptor (section)

== Types ==

=== CB<sub>1</sub> ===
{{Main|Cannabinoid receptor type 1}}

Cannabinoid receptor type 1 (CB<sub>1</sub>) receptors are thought to be one of the most widely [[Gene expression|expressed]] G<sub>αi</sub> protein-coupled receptors in the brain. One mechanism through which they function is endocannabinoid-mediated [[depolarization-induced suppression of inhibition]], a very common form of [[retrograde signaling]], in which the depolarization of a single neuron induces a reduction in [[GABA]]-mediated neurotransmission. Endocannabinoids released from the depolarized post-synaptic neuron bind to CB<sub>1</sub> receptors in the pre-synaptic neuron and cause a reduction in GABA release due to limited presynaptic calcium ions entry.{{medcn|date=December 2017}}

They are also found in other parts of the body. For instance, in the liver, activation of the CB<sub>1</sub> receptor is known to increase de novo [[lipogenesis]].<ref name="pmid15864349"/>

=== CB<sub>2</sub> ===
{{Main|Cannabinoid receptor type 2}}

[[Cannabinoid receptor 2 (macrophage)|CB<sub>2</sub>]] receptors are expressed on [[T cell]]s of the [[immune system]], on [[macrophage]]s and [[B cell]]s, in [[Pluripotential hemopoietic stem cell|hematopoietic cells]], and in the brain and CNS (2019).<ref>{{cite book |vauthors=Onaivi J |chapter=Endocannabinoid System Components: Overview and Tissue Distribution |chapter-url=https://doi.org/10.1007/978-3-030-21737-2_1 |title=Recent Advances in Cannabinoid Physiology and Pathology |veditors=Bukiya A |publisher=Springer |location=Cham. |series=Advances in Experimental Medicine and Biology |year=2019 |volume=1162 |pages=1–12 |doi=10.1007/978-3-030-21737-2_1 |pmid=31332731 |isbn=978-3-030-21736-5 |s2cid=198172390 |access-date=19 October 2021 |archive-date=20 April 2023 |archive-url=https://web.archive.org/web/20230420210524/https://link.springer.com/chapter/10.1007/978-3-030-21737-2_1 |url-status=live }}</ref> They also have a function in [[keratinocyte]]s. They are also expressed on peripheral [[nerve]] terminals. These receptors play a role in [[antinociception]], or the relief of [[pain]]. In the brain, they are mainly expressed by [[Microglia|microglial cells]], where their role remains unclear. While the most likely cellular targets and executors of the CB<sub>2</sub> receptor-mediated effects of endocannabinoids or synthetic agonists are the immune and immune-derived cells (e.g. [[leukocytes]], various populations of T and B lymphocytes, [[Monocyte|monocytes]]/[[Macrophage|macrophages]], [[Dendritic cell|dendritic cells]], [[Mast cell|mast cells]], microglia in the brain, [[Kupffer cell|Kupffer cells]] in the liver, [[Astrocyte|astrocytes]], etc.), the number of other potential cellular targets is expanding, now including endothelial and smooth muscle cells, fibroblasts of various origins, cardiomyocytes, and certain neuronal elements of the peripheral or central nervous systems (2011).<ref name="pmid21295074"/>

=== Other ===
The existence of additional cannabinoid receptors has long been suspected, due to the actions of compounds such as [[abnormal cannabidiol]] that produce cannabinoid-like effects on [[blood pressure]] and [[inflammation]], yet do not activate either CB<sub>1</sub> or CB<sub>2</sub>.<ref name="pmid10570211"/><ref name="pmid17965195"/> Recent research strongly supports the hypothesis that the ''N''-arachidonoyl glycine ([[NAGly]]) receptor [[GPR18]] is the molecular identity of the abnormal cannabidiol receptor and additionally suggests that NAGly, the endogenous lipid metabolite of [[anandamide]] (also known as arachidonoylethanolamide or AEA), initiates directed [[Microglia#Chemokines|microglial migration]] in the CNS through activation of [[GPR18]].<ref name="pmid20346144"/> Other molecular biology studies have suggested that the orphan receptor [[GPR55]] should in fact be characterised as a cannabinoid receptor, on the basis of sequence homology at the binding site. Subsequent studies showed that GPR55 does indeed respond to cannabinoid ligands.<ref name="pmid17876302"/><ref name="pmid17704827"/> This profile as a distinct non-CB<sub>1</sub>/CB<sub>2</sub> receptor that responds to a variety of both endogenous and exogenous cannabinoid ligands, has led some groups to suggest GPR55 should be categorized as the CB<sub>3</sub> receptor, and this re-classification may follow in time.<ref name="pmid16517404"/> However this is complicated by the fact that another possible cannabinoid receptor has been discovered in the [[hippocampus]], although its gene has not yet been cloned,<ref name="pmid18482429"/> suggesting that there may be at least two more cannabinoid receptors to be discovered, in addition to the two that are already known. [[GPR119]] has been suggested as a fifth possible cannabinoid receptor,<ref name="pmid17906678"/> while the [[PPAR]] family of nuclear hormone receptors can also respond to certain types of cannabinoid.<ref>{{cite journal | vauthors = O'Sullivan SE | title = An update on PPAR activation by cannabinoids | journal = British Journal of Pharmacology | volume = 173 | issue = 12 | pages = 1899–910 | date = June 2016 | pmid = 27077495 | pmc = 4882496 | doi = 10.1111/bph.13497 }}</ref>