scholarly journals The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3160
Author(s):  
Joseph Bouskila ◽  
Maxime Bleau ◽  
Catarina Micaelo-Fernandes ◽  
Jean-François Bouchard ◽  
Maurice Ptito
Keyword(s):  
G Protein ◽  
Visual Information ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Expression Patterns ◽  
Retinal Function ◽  
Age Related Macular Degeneration ◽  
Transient Receptor Potential Vanilloid ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

The endocannabinoid (eCB) system has been found in all visual parts of the central ner-vous system and plays a role in the processing of visual information in many species, including monkeys and humans. Using anatomical methods, cannabinoid receptors are present in the monkey retina, particularly in the vertical glutamatergic pathway, and also in the horizontal GABAergic pathway. Modulating the eCB system regulates normal retinal function as demonstrated by electrophysiological recordings. The characterization of the expression patterns of all types of cannabinoid receptors in the retina is progressing, and further research is needed to elucidate their exact role in processing visual information. Typical cannabinoid receptors include G-protein coupled receptor CB1R and CB2R, and atypical cannabinoid receptors include the G-protein coupled receptor 55 (GPR55) and the ion channel transient receptor potential vanilloid 1 (TRPV1). This review focuses on the expression and localization studies carried out in monkeys, but some data on other animal species and humans will also be reported. Furthermore, the role of the endogenous cannabinoid receptors in retinal function will also be presented using intraocular injections of known modulators (agonists and antagonists) on electroretinographic patterns in monkeys. The effects of the natural bioactive lipid lysophosphatidylglucoside and synthetic FAAH inhibitor URB597 on retinal function, will also be described. Finally, the potential of typical and atypical cannabinoid receptor acti-vity regulation in retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinitis pigmentosa will be briefly explored.

scholarly journals Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5186 ◽  
Author(s):  
Serena Silvestro ◽  
Giovanni Schepici ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
G Protein ◽  
Serotonin Receptor ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Neurological Diseases ◽  
In Vivo Studies ◽  
Receptor Subtype ◽  
Transient Receptor Potential Vanilloid ◽  
Neuroprotective Effects ◽  
G Protein Coupled

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid known for its beneficial effects including antioxidant and anti-inflammatory properties. Moreover, CBD is a compound with antidepressant, anxiolytic, anticonvulsant and antipsychotic effects. Thanks to all these properties, the interest of the scientific community for it has grown. Indeed, CBD is a great candidate for the management of neurological diseases. The purpose of our review is to summarize the in vitro and in vivo studies published in the last 15 years that describe the biochemical and molecular mechanisms underlying the effects of CBD and its therapeutic application in neurological diseases. CBD exerts its neuroprotective effects through three G protein coupled-receptors (adenosine receptor subtype 2A, serotonin receptor subtype 1A and G protein-coupled receptor 55), one ligand-gated ion channel (transient receptor potential vanilloid channel-1) and one nuclear factor (peroxisome proliferator-activated receptor γ). Moreover, the therapeutical properties of CBD are also due to GABAergic modulation. In conclusion, CBD, through multi-target mechanisms, represents a valid therapeutic tool for the management of epilepsy, Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.

scholarly journals The Habenular Receptor GPR151 Regulates Addiction Vulnerability Across Drug Classes

2019 ◽  
Author(s):  
Beatriz Antolin-Fontes ◽  
Kun Li ◽  
Jessica L. Ables ◽  
Michael H. Riad ◽  
Andreas Görlich ◽  
...  
Keyword(s):  
G Protein ◽  
Cannabinoid Receptors ◽  
Behavioral Responses ◽  
G Protein Coupled Receptor ◽  
Inhibitory Protein ◽  
Vesicle Release ◽  
Release Probability ◽  
Drug Classes ◽  
G Protein Coupled ◽  
Camp Levels

SUMMARYThe habenula controls the addictive properties of nicotine but also densely expresses opioid and cannabinoid receptors. As such, identification of strategies to manipulate habenular activity may yield new approaches to treat substance use disorders. Here we show that GPR151, an orphan G protein-coupled receptor (GPCR) highly enriched in the habenula of humans and rodents plays a critical role in regulating habenular function and behavioral responses to addictive drugs. We show that GPR151 is expressed on axonal and presynaptic membranes and synaptic vesicles, and regulates synaptic fidelity and plasticity. We find that GPR151 associates with synaptic components controlling vesicle release and ion transport and couples to the G-alpha inhibitory protein Gαo1to reduce cAMP levels. Stable cell lines expressing GPR151 confirm that it signals via Gi/o and are amenable to ligand screens.Gpr151null mice show diminished behavioral responses to nicotine, and self-administer greater quantities of the drug, phenotypes rescued by viral re-expression ofGpr151in the habenula.Gpr151null mice are also insensitive to the behavioral actions of morphine and cannabinoids. These data identify GPR151 as a critical modulator of habenular function that controls addiction vulnerability across different drug classes.HighlightsHabenula neurons are enriched in nicotinic, opioid, cannabinoid and GPR151 receptorsGPR151 modulates synaptic fidelity and release probability at habenular terminals.Habenular GPR151 plays a role in drug abuse and food intake/weight controlGPR151 couples to the G-alpha inhibitory protein Gαo1to reduce cAMP levels.eTOC BlurbAntolin-Fontes at al. identify a G protein-coupled receptor, GPR151, which is highly enriched in human habenular neurons. These neurons are primarily enriched with nicotinic, opioid and cannabinoid receptors. We find that GPR151 modulates habenular synaptic vesicle release probability and behavioral responses to these drugs of abuse.

Developmental and adult expression patterns of the G-protein-coupled receptor GPR88 in the rat: Establishment of a dual nuclear-cytoplasmic localization

2016 ◽  
Vol 524 (14) ◽  
pp. 2776-2802 ◽  
Author(s):  
Renaud Massart ◽  
Virginie Mignon ◽  
Jennifer Stanic ◽  
Paola Munoz-Tello ◽  
Jerôme A.J. Becker ◽  
...  
Keyword(s):  
G Protein ◽  
Expression Patterns ◽  
Cytoplasmic Localization ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Single-Cell Transcriptomic Evidence for Dense Intracortical Neuropeptide Networks

2019 ◽  
Author(s):  
Stephen J Smith ◽  
Uygar Sümbül ◽  
Lucas Graybuck ◽  
Forrest Collman ◽  
Sharmishtaa Seshamani ◽  
...  
Keyword(s):  
Single Cell ◽  
G Protein ◽  
Cortical Neurons ◽  
Expression Patterns ◽  
List Type ◽  
Neuron Type ◽  
Sequencing Data ◽  
G Protein Coupled Receptor ◽  
Neocortical Neurons ◽  
G Protein Coupled

SummarySeeking new insights into the homeostasis, modulation and plasticity of cortical synaptic networks, we have analyzed results from a single-cell RNA-seq study of 22,439 mouse neocortical neurons. Our analysis exposes transcriptomic evidence for dozens of molecularly distinct neuropeptidergic modulatory networks that directly interconnect all cortical neurons. This evidence begins with a discovery that transcripts of one or more neuropeptide precursor (NPP) and one or more neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes are highly abundant in all, or very nearly all, cortical neurons. Individual neurons express diverse subsets of NP signaling genes from palettes encoding 18 NPPs and 29 NP-GPCRs. These 47 genes comprise 37 cognate NPP/NP-GPCR pairs, implying the likelihood of local neuropeptide signaling. Here we use neuron-type-specific patterns of NP gene expression to offer specific, testable predictions regarding 37 peptidergic neuromodulatory networks that may play prominent roles in cortical homeostasis and plasticity.ImpactSingle-cell mRNA sequencing data from mouse neocortex expose evidence for peptidergic neuromodulatory networks that locally interconnect every cortical neuronData HighlightsAt least 97% of mouse neocortical neurons express one or more of 18 neuropeptide precursor proteins (NPP) genes at very high levelsAt least 98% of cortical neurons express one or more of 29 neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes cognate to the 18 highly expressed NPP genesNeocortical expression of these 18 NPP and 29 NP-GPCR genes is highly neuron-type-specific and their expression patterns differentiate transcriptomic neuron types with exceptional powerNeuron-type taxonomy and type-specific expression of 37 cognate NPP / NP-GPCR gene pairs generate testable predictions of at least 37 local intracortical neuromodulation networks

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