Cannabinoid receptor

src: molpharm.aspetjournals.org

The Cannabinoid receptor , located throughout the body, is part of the endocannabinoid system, which is involved in various physiological processes including appetite, pain sensation, mood, and memory.

The Cannabinoid Receptor is a class of cell membrane receptors in superfamily of G paired protein receptors. Like a typical G protein paired receptor, the cannabinoid receptors contain seven domains that include transmembranes. Cannabinoid receptors are activated by three main groups of ligands: endocannabinoids, produced by the mammillary body; plant cannabinoids (such as cannabidiol, produced by cannabis plants); and synthetic cannabinoids (such as HU-210). All endocannabinoids and plant cannabinoids are lipophilic, such as fat-soluble compounds.

There are currently two known cannabinoid receptor subtypes, called CB ₁ and CB ₂ . The receptor CB ₁ is expressed primarily in the brain (the central nervous system or "CNS"), but also in the lungs, liver and kidneys. The CB receptor ₂ is expressed primarily in the immune system and hematopoietic cells. The mounting evidence shows that there are new cannabinoid receptors, non-CB ₁ and non-CB ₂ , expressed in endothelial cells and on CNS. In 2007, the binding of some cannabinoids to the G protein-coupled GPR55 receptors in the brain has been described.

The sequence of recipe protein CB ₁ and CB ₂ was about 44% similar. When only transmembrane areas of the receptor are considered, the amino acid similarity between two receptor subtypes is about 68%. In addition, minor variations in each of the receptors have been identified. The cannabinoids are reversible and stereo-selective binding to cannabinoid receptors. Selective subnypes of selective cannabinoids have been developed that might theoretically have advantages for the treatment of certain diseases such as obesity.

It seems that the cannabinoid receptors are unique to Chordata phyla and, thus, they have a rather limited phylogenetic distribution in the animal kingdom. However, enzymes involved in endocannabinoid biosynthesis/inactivation and general endocannabinoid signaling (involving targets other than CB1/2 type receptors) occur throughout the animal kingdom.

Video Cannabinoid receptor

CB ₁

1st receptor receptor (CB ₁ ) Cannabinoid receptors are considered to be one of the receptor protein receptor G _{? I} is the most widely expressed in the brain. This is caused by endozannabinoid-mediated depolarization induced suppression of inhibition, a very common form of retrograde signaling, in which the depolarization of one neuron induces a decrease in GABA-mediated neurotransmission. Endocannabinoids released from post-synaptic synaptic neurons bind to receptor CB ₁ in pre-synaptic neurons and cause a decrease in GABA release due to limited presinaptic calcium ion entries.

They are also found in other parts of the body. For example, in the liver, activation of CB receptors ₁ is known to increase de novo lipogenesis.

A 2004 study showed that their endocannabinoids and cannabinoid receptors play a major role during development before and after birth. In another recent study a group of researchers combined a stochastic optical reconstruction microscope (STORM) and a patch clamp to see the distribution of CB1 at the nanoscale with exceptional resolution.

Maps Cannabinoid receptor

CB ₂

CB receptors ₂ are mainly expressed on T cells of the immune system, in macrophages and B cells, and in hematopoietic cells. They also have a function in keratinocytes. They are also expressed on peripheral nerve terminals. These receptors play a role in antinociception, or relieve pain. In the brain, they are mainly expressed by microglial cells, where their role remains unclear. While the largest cellular and acting targets of the receptor-mediated endokannabinoid or synthetic CB-2 sub-karbondi synthetic agonists are immune-derived cells and immune-derived cells (eg leukocytes, populations of T and B lymphocytes, monocytes/macrophages, dendritic cells, cells mast, microglia in the brain, Kupfer liver cells, astrocytes, etc.), the number of other potential cellular targets develops, now including endothelial and smooth muscle cells, fibroblasts of various origins, cardiomyocytes, and certain neuronal elements of the peripheral or central nervous system.

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Other cannabinoid receptors

The presence of additional cannabinoid receptors has long been suspected, due to the action of compounds such as abnormal cannabidiols that produce effects such as cannabinoids in blood pressure and inflammation, but do not activate CB ₁ or CB ₂ . The latest study strongly supports the hypothesis that the GPR18 receptor (GH) is a molecular identity of abnormal cannabidiol receptors and additionally shows that NAGly, an endogenous lipid metabolite anandamide (also known as arachidonoylethanolamide). or AEA), initiating microglial migrations directed at the CNS through activation of GPR18. Other molecular biology studies have suggested that GPR55 orphan receptors should in fact be characterized as cannabinoid receptors, based on the homology sequence on the binding sites. Further studies show that GPR55 does indeed respond to a cannabinoid ligand. This profile as a non-CB recipe ₁ /CB ₂ that responds to a variety of endogenous and exogenous cannabinoid ligands, has led some groups to suggest GPR55 should be categorized as CB ₃ , and this re-classification can follow the time. But this is complicated by the fact that other cannabinoid receptors that may have been found in the hippocampus, although their genes have not been cloned, suggest that there may be at least two cannabinoid receptors to be found, in addition to two known ones. GPR119 has been proposed as the fifth possible cannabinoid receptor.

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Signaling

Cannabinoid receptors are activated by cannabinoids, produced naturally in the body (endocannabinoids) or put into the body as marijuana or related synthetic compounds.

Once the receptor is involved, multiple intracellular signal transduction pathways are activated. Initially, it is thought that cannabinoid receptors primarily inhibit the enzyme adenylate cyclase (and thus the production of second cyclic AMP messenger molecules), and positively affect the potassium channel in the liver (= Kir or IRK). However, a much more complex picture has emerged in different cell types, involving other potassium ion channels, calcium channels, protein kinases A and C, Raf-1, ERK, JNK, p38, c-fos, c-jun and more.

The separation between the therapeutically undesirable psychotropic effects, and which are clinically desirable, however, has not been reported with agonists binding to cannabinoid receptors. THC, as well as the two major endogen compounds identified so far that bind to the cannabinoid --anandamide and 2-arachidonylglycerol (2-AG) receptors - produce most of the effect by binding to CB ₁ and CB ₂ cannabinoid receptors. While the effects mediated by CB ₁ , mostly in the central nervous system, have been thoroughly investigated, those mediated by CB ₂ are not well defined.

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Physiology

Cardiovascular activity

Studies have suggested that activation of CB receptors ₁ on human and rodent cardiomyocytes, coronary artery endothelial cells and inflammatory cells increased activation of mitogen-active (MAP) kinase p38 and JNK, formation of reactive oxygen species, cell death , and inflammatory cardiovascular responses both in vitro, as well as in models of heart failure, atherosclerosis and vascular inflammation.

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Cannabinoid Treatment

Synthetic Tetrahydrocannabinol (THC) is prescribed under INN dronabinol or brand name Marinol , to treat vomiting and to increase appetite, especially in people with AIDS as well as for refractory nausea and vomiting in people who underwent chemotherapy. THC is also an active ingredient in nabiximols, a Cannabis-specific extract approved as a botanical drug in the UK in 2010 as an oral spray for people with multiple sclerosis to relieve neuropathic pain, spasticity, overactive bladder, and other symptoms.

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Ligans

See also: cannabinoid receptor type 1 ligand, lymph node 2 ligand receptor

Binding and selectivity of cannabinoid ligands

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See also

• Cannabinoid receptor antagonist
• Added endokannabinoid
• Endocannabinoid reuptake inhibitor
• Cannabidiol
• The effects of cannabis

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References

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External links

• Cannabinoid Receptors at the National Library of Medicine US Subject of Medical Subject (MeSH)
• The Endocannabinoid System Network (ECSN) - CB ₁ receptor
• "Cannabinoid Receptors". IUPHAR Database from Receptor and Ion Channel . International Union of Basic and Clinical Pharmacology.

Source of the article : Wikipedia