Navarro Gemma, et al.
Pharmacological Research, 2020
Abstract
Background
Recent approved medicines whose active principles are Δ9Tetrahidrocannabinol (Δ9-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available. Mode of action of cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabidivarin (CBDV) and cannabigerivarin (CBGV) is, to the very least, partial. Hypothesis/
Purpose
Cannabinoid CB1 or CB2 receptors, which belong to the G-protein-coupled receptor (GPCR) family, are important mediators of the action of those cannabinoids. Pure CBG, CBDA, CBGA, CBDV and CBGV from Cannabis sativa L. are differentially acting on CB1 or CB2 cannabinoid receptors.
Study design
Determination of the affinity of phytocannabinoids for cannabinoid receptors and functional assessment of effects promoted by these compounds when interacting with cannabinoid receptors.
Methods
A heterologous system expressing the human versions of CB1 and/or CB2 receptors was used. Binding to membranes was measured using radioligands and binding to living cells using a homogenous time resolved fluorescence resonance energy transfer (HTRF) assay. Four different functional outputs were assayed: determination of cAMP levels and of extracellular-signal-related-kinase phosphorylation, label-free dynamic mass redistribution (DMR) and ß-arrestin recruitment.
Results
Affinity of cannabinoids depend on the ligand of reference and may be different in membranes and in living cells. All tested phytocannabinoids have agonist-like behavior but behaved as inverse-agonists in the presence of selective receptor agonists. CBGV displayed enhanced potency in many of the functional outputs. However, the most interesting result was a biased signaling that correlated with differential affinity, i.e. the overall results suggest that the binding mode of each ligand leads to specific receptor conformations underlying biased signaling outputs.
Conclusion
Results here reported and the recent elucidation of the three-dimensional structure of CB1 and CB2 receptors help understanding the mechanism of action that might be protective and the molecular drug-receptor interactions underlying biased signaling.
Keywords
Biased signaling; Cytocrin; GPCR structure; Homogeneous binding; Phytocannabinoids; Radioligand binding.
Copyright © 2020 Elsevier Ltd. All rights reserved.
| PMID: | 32470563 |
|---|---|
| DOI: | 10.1016/j.phrs.2020.104940 |
| Category: | General properties of Cannabidiol |
| Category: | General properties of Cannabidiolic Acid |
| Category: | General properties of Cannabidivarin |
| Category: | General properties of Cannabigerol |
| Category: | General properties of Cannabigerolic Acid |
| Category: | General properties of Cannabigerivarin |
Articles similar to "Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB 1, CB 2 and CB 1/CB 2 heteromer receptors."
- The properties of Cannabidiol: The cannabinoid system and immune modulation. (Studies on the effects of marijuana smoking have evolved into the discovery and description of the endocannabinoid system...)
- The properties of Cannabidiol: Medicinal Uses of Marijuana and Cannabinoids. (In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC)...)
- The properties of Cannabidiol: Cannabidiol Reduces Neuroinflammation and Promotes Neuroplasticity and Functional Recovery After Brain Ischemia. (This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice...)
- The properties of Cannabidiolic Acid: Cannabis Therapeutics and the Future of Neurology. (Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes...)
- The properties of Cannabigerol: Nonpsychotropic cannabinoids, abnormal cannabidiol and canabigerol-dimethyl heptyl, act at novel cannabinoid receptors to reduce intraocular pressure. (The objective of our study was to examine the pharmacology of the intraocular pressure (IOP)-lowering actions of the behaviorally inactive cannabinoids, abnormal cannabidiol (abn-CBD), and a cannabigerol analog, cannabigerol-dimethyl heptyl (CBG-DMH), in comparison to that of the nonselective cannabinoid 1 receptor (CB(1)R) and CB(2)R agonist, WIN55,212-2, in Brown Norway rats...)
- The properties of Cannabigerol: Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA). (Hemp seed oil from Cannabis sativa L...)
- The properties of Cannabidivarin: Cannabis sativa: Much more beyond Δ 9-tetrahydrocannabinol. (Cannabis is the most used illicit drug worldwide and its medicinal use is under discussion, being regulated in several countries...)
- The properties of Cannabigerol: Molecular Pharmacology of Phytocannabinoids. (Cannabis sativa has been used for recreational, therapeutic and other uses for thousands of years...)
- The properties of Cannabigerivarin: A systematic review of minor phytocannabinoids with promising neuroprotective potential. (Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol (CBD) and Δ9 -tetrahydrocannabinol, including Δ9 -tetrahydrocannabinolic acid, Δ9 -tetrahydrocannabivarin, cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerivarin (CBGV), cannabigerovarinic acid, cannabichromevarinic acid (CBCVA), cannabidivarinic acid (CBDVA), and cannabinol (CBN)...)
- The properties of Cannabidivarin: Pharmacology of cannabinoids in the treatment of epilepsy. (The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use...)
- The properties of Cannabidiol: Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. (Increasing interest in the biology, chemistry, pharmacology, and toxicology of cannabinoids and in the development of cannabinoid medications necessitates an understanding of cannabinoid pharmacokinetics and disposition into biological fluids and tissues...)
- The properties of Cannabidiol: Cannabidiol (CBD). (Cannabis sativa or Indian hemp (subfamily Cannaboideae of family Moraceae) is an annual herbaceous plant, native to central and western Asia, cultivated for medicinal properties and for hemp, which is a natural textile fiber...)
- The properties of Cannabidiol: Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. (Exogenous cannabinoids are structurally and pharmacologically diverse compounds that are widely used...)
- The properties of Cannabigerol: Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L. (Chemical investigation of the pollen grain collected from male plants of Cannabis sativa L...)
- The properties of Cannabidivarin: Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. (Background and purpose: Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures...)
- The properties of Cannabigerol: The Pharmacological Case For Cannabigerol (CBG). (Medical cannabis and individual cannabinoids, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), are receiving growing attention in both the media and the scientific literature...)
- The properties of Cannabigerol: Cannabigerol Action at Cannabinoid CB 1 and CB 2 Receptors and at CB 1-CB 2 Heteroreceptor Complexes. (Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L...)
- The properties of Cannabigerol: A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis. (Phytocannabinoids like ∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms...)