“The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer.
Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.”
“Ligands targeting G protein-coupled receptors (GPCR) expressed by microglia have been shown to regulate distinct components of their activation process, including cell proliferation, migration and differentiation into M1 or M2 phenotypes.
Cannabinoids, including the active component of the Cannabis plant, tetrahydrocannabinol (THC), and the synthetic alkylindole (AI) compound, WIN55212-2 (WIN-2), activate two molecularly identified GPCRs: CB1 and CB2 .
Our results suggest that microglia express functional AI-sensitive receptors that control select components of their activation process.
Agonists of these novel targets might represent a novel class of therapeutics to influence the microglial cell activation process. ”
“The two main receptors of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and 2 (CB2R) were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors.
CB1R and CB2R activity influences signal Cascades, which are known to play a role in the regulation of the cellular “self-digestion” process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the autophagic activity directly.
In the recent years, several scientific reports demonstrate an involvement of CB1R and CB2R signaling in the control of the autophagic activity in different paradigms.
In this review, we summarize the recent literature on this topic, which is in part contradictory and therefore, it is of great importance to illuminate the results of the single reports in the physiological context of the model systems used in these studies.
Utilizing CB1R and CB2R as pharmacological targets to modulate the autophagic activity is a promising treatment strategy for the treatment of different patho-physiological conditions and disease.”
“Endocannabinoids and their G protein-coupled receptors have been suggested to play a key role in human pregnancy, by regulating important aspects such as implantation, decidualization, placentation and labor.
G protein-coupled receptor 55 (GPR55) was previously postulated to be another cannabinoid receptor, since specific cannabinoids were shown to act independently of the classical cannabinoid receptors CB1 or CB2.
Current knowledge about GPR55 expression and function in human placenta is very limited and motivated us to evaluate human placental GPR55 expression in relation to other human peripheral tissues and to analyze spatiotemporal GPR55 expression in human placenta.
Gene expression analysis revealed low GPR55 levels in human placenta, when compared to spleen and lung, the organs showing highest GPR55 expression.
Moreover, expression analysis showed 5.8 fold increased placental GPR55 expression at term compared to first trimester. Immunohistochemistry located GPR55 solely at the fetal endothelium of first trimester and term placentas. qPCR and immunocytochemistry consistently confirmed GPR55 expression in isolated primary placental arterial and venous endothelial cells. Incubation with L-α-lysophosphatidylinositol (LPI), the specific and functional ligand for GPR55, at a concentration of 1 µM, significantly enhanced migration of venous, but not arterial endothelial cells.
LPI-enhanced migration was inhibited by the GPR55 antagonist O-1918, suggesting a role of the LPI-GPR55 axis in placental venous endothelium function.”
The effects of cannabinoids have been known for centuries and over the past several decades two G-protein coupled receptors, CB1 and CB2, have been identified that are responsible for their activity.
Endogenous lipid-derived cannabinergic agents have been found, biosynthetic and catabolic machinery characterized, and synthetic agents have been designed to modulate these receptors.
Selective agents including agonists, antagonists, inverse agonists and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone.
As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated.
The CB1 receptor while ubiquitous is densely expressed in the brain and CB2 is largely found on cells of immune origin.
This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability.
In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic β-cells, insulin resistance and feeding behavior leading toward obesity.
The role of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converges at inflammatory cell activation thereby providing an opportunity for intervention.
Lastly, CB2 modulation is discussed in the context of an experimental model of post-menopausal osteoporosis.
Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.”
“The endocannabinoid system (ECS) is defined as the signalling system composed of: (1) the two G‐protein‐coupled receptors known as cannabinoid receptors of type‐1 and ‐2 (CB1 and CB2); (2) the two most studied endogenous agonists of such receptors, the endocannabinoids anandamide (N‐arachidonoyl‐ethanolamine) and 2‐AG (2‐arachidonoyl‐glycerol); (3) enzymes and other proteins regulating the tissue levels of endocannabinoids; and (4) enzymes and other proteins that, together with endocannabinoids, regulate the activity of cannabinoid receptors.
A key role of the ECS is emerging in the control not only of central and peripheral nervous system functions, but also of most aspects of mammalian physiology, including energy intake, processing and storage, the immune response, reproduction and cell fate.
The ECS is also subject to dysregulation, and this seems to contribute to the symptoms and progress of several diseases. Hence, the possibility of developing new therapies starting from our increasing knowledge of the ECS is discussed.”
http://www.els.net/WileyCDA/ElsArticle/refId-a0023403.html
http://www.thctotalhealthcare.com/category/endocannabinoid-system/
“Since the identification of the endocannabinoid system, two G protein-coupled receptors (GPCRs) of this complex system were identified and characterized: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R).
In addition to orthosteric and subsequently allosteric ligands, new strategies have been used to target CBRs.
Bivalent ligands and multifunctional ligands acting at diverse biological targets have been designed, synthesized, and characterized for both CBRs. Due to their altered receptor binding and pharmacological profiles, they are interesting tools to explore CBR functions and their interactions with other physiological systems.
Moreover, this approach may bear therapeutic advantages in the therapy of CBR-related disorders, especially multifactorial diseases.
Promising prospects include anorectics with fewer side effects, analgesics with decreased tolerance, and therapeutics with multiple pharmacological activities for the treatment of cancer, inflammation, multiple sclerosis, Huntington’s and Alzheimer’s diseases.”
“The endocannabinoid system (ECS) comprises the two well characterized Gi/o -protein coupled receptors (CB1, CB2), their endogenous lipid ligands and the enzymes involved in their biosynthesis and biotransformation.
Drug discovery efforts relating to the ECS have been focused mainly on the two cannabinoid receptors and the two endocannabinoid deactivating enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL).
This review provides an overview of cannabinergic agents used in drug research and those being explored clinically.”
“Synthetic cannabinoids, the psychoactive components of the Cannabis sativa (marijuana) and their endogenous counterparts, act through two G protein-coupled receptors, CB1 and CB2.
The endocannabinoids are metabolized by fatty acid amide hydrolase (FAAH).
We have examined CB1 receptor and FAAH expression in human term placenta by immunohistochemistry.
CB1 receptor was found to be present in all layers of the membrane, with particularly strong expression in the amniotic epithelium and reticular cells and cells of the maternal decidua layer. Moderate expression was observed in the chorionic cytotrophoblasts. The expression of FAAH was the highest in amniotic epithelial cells, chorionic cytotrophoblast and maternal decidua layer.
Our results suggest that the human placenta is a likely target for cannabinoid action and metabolism. ”
“Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others.
Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract.
These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut.
…the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field.
Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency.
The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.”