CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum

Martínez‐Pinilla, Eva; Reyes‐Resina, Irene; Oñatibia-Astibia, Ainhoa; Zamarbide, Marta; Ricobaraza, Ana; Navarro, Gemma; Moreno, Estefanía; Dopeso‐Reyes, Iria G.; Sierra, Salvador; Rico, Alberto J.; Roda, Elvira; Lanciego, José L.; Franco, Rafael

doi:10.1016/j.expneurol.2014.06.017

Cited by 81 publications

(64 citation statements)

References 46 publications

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“…In particular: 1) the orphan GPCR, GPR55, has been suggested to act as target for both cannabinoids, that is, THC and CBD, which seem to act as agonist and antagonist, respectively, for this receptor [42], and N-palmitoylethanolamine, which seems to be an agonist [42]. In fact, there is controversial evidence that anandamide and 2-AG may also activate GPR55, and the recent finding of CB1-GPR55 heteromers might explain why some authors have found that the 2 endocannabinoids directly activate this orphan GPCR and most others have not [43][44][45][46]. Another orphan GPCR, GPR18, is instead activated by N-arachidonoyl-glycine and by a synthetic CBD analogue known as abnormal-cannabidiol [47,48].…”

Section: Other Ways Through Which Non-thc Plant Cannabinoids Influencmentioning

confidence: 99%

The Endocannabinoid System and its Modulation by Phytocannabinoids

2015

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The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ 9 -tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)-cannabinoid receptor type-1 (CB 1 R) and cannabinoid receptor type-2 (CB 2 R); their two most studied endogenous ligands, the "endocannabinoids" N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB 1 R and CB 2 R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with "endocannabinoid-like" mediators that may or may not interact with the same proteins as Δ 9 -tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true "endocannabinoidome", discovered after the cloning of CB 1 R and CB 2 R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids.

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Section: Other Ways Through Which Non-thc Plant Cannabinoids Influencmentioning

confidence: 99%

The Endocannabinoid System and its Modulation by Phytocannabinoids

2015

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“…GPR55 can form heteromers with CB 1 R or CB 2 R to elicit different pathways via ligand- and concentration-specific crosstalk (Balenga et al, 2011, 2014; Kargl et al, 2012; Martínez-Pinilla et al, 2014). Heteromers of CB 1 R and GPR55 are reported in CNS (Martínez-Pinilla et al, 2014) and Human Embryonic Kidney cell lines (Kargl et al, 2012). CB 1 R inhibits GPR55 signaling when they are co-expressed on a cell (Kargl et al, 2012).…”

Section: Ecs In Sepsismentioning

confidence: 99%

CB2 and GPR55 Receptors as Therapeutic Targets for Systemic Immune Dysregulation

et al. 2016

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The endocannabinoid system (ECS) is involved in many physiological processes and has been suggested to play a critical role in the immune response and the central nervous system (CNS). Therefore, ECS modulation has potential therapeutic effects on immune dysfunctional disorders, such as sepsis and CNS injury-induced immunodeficiency syndrome (CIDS). In sepsis, excessive release of pro- and anti-inflammatory mediators results in multi-organ dysfunction, failure, and death. In CIDS, an acute CNS injury dysregulates a normally well-balanced interplay between CNS and the immune system, leading to increased patients’ susceptibility to infections. In this review, we will discuss potential therapeutic modulation of the immune response in sepsis and CNS injury by manipulation of the ECS representing a novel target for immunotherapy.

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“…Indeed, there is controversy regarding the effects of endocannabinoids and congeners at GRP55, due to the different results obtained with different functional assays in various biological systems (786). It is possible that different biased signaling properties of these ligands, and tissue and celldependent coupling of GPR55 with different G proteins and effector systems, or with CB1 or CB2 in heteromers, all contribute to this heterogeneity of results (110,537,592).…”

Section: B Other Receptors For Endocannabinoidsmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

366

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum

Cited by 81 publications

References 46 publications

The Endocannabinoid System and its Modulation by Phytocannabinoids

The Endocannabinoid System and its Modulation by Phytocannabinoids

CB2 and GPR55 Receptors as Therapeutic Targets for Systemic Immune Dysregulation

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

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