Phytoplant | Potentiation of cannabinoid signaling in microglia by adenosine A2A receptor antagonists

Potentiation of cannabinoid signaling in microglia by adenosine A2A receptor antagonists

Introduction

Neuroprotective M2-skewed microglia appear as promising to alter the course of neurodegenerative diseases and G protein-coupled receptors (GPCRs) are potential targets to achieve such microglial polarization. A common feature of adenosine A2A (A2AR) and cannabinoid CB2 (CB2R) GPCRs in microglia is that their expression is upregulated in Alzheimer's disease (AD).

Material and méthods

Δ9-THC was purified from the Cannabis variety MONIEK (CPVO/20160114) following a patented method described in the Phytoplant Patents: “Methods of purifying cannabinoids using liquid: liquid chromatography” with code 10207199 B2. The Δ9-THC has a purity > 95%. CANNA products were used for the cultivation process.

Results

CB2R seems a target for neuroprotection, delaying neurodegenerative processes like those associated to AD or Parkinson's diseases. A2AR antagonists reduce amyloid burden and improve cognitive performance and memory in AD animal models. We here show a close interrelationship between these two receptors in microglia; they can physically interact and affect the signaling of each other, likely due to conformational changes within the A2A-CB2 receptor heteromer (A2A-CB2Het). Particularly relevant is the upregulation of A2A-CB2Het expression in samples from the APPSw,Ind AD transgenic mice model. The most relevant finding, confirmed in both heterologous cells and in primary cultures of microglia, was that blockade of A2A receptors results in increased CB2R-mediated signaling.

Discusion

This heteromer-specific feature suggests that A2AR antagonists would potentiate, via microglia, the neuroprotective action of endocannabinoids with implications for AD therapy.

Go to the publication

Other publications

First Report of Charcoal Rot Caused by Macrophomina phaseolina on Hemp (Cannabis sativa L.) Varieties Cultivated in Southern Spain

Development of ornamental Cannabis sativa L. cultivars: phytochemical, morphological, genetic characterization and propagation aspects

Influence of media composition and genotype for successful Cannabis sativa L. in vitro introduction

Yield of new hemp varieties for medical purposes in a semi-arid Mediterranean environment (Spain)

Cannabinoids and terpenoids yields of the ornamental Cannabis sativa L. cultivar ‘Divina’ characterized by a variegated foliage as morphological marker

Cannabidiol Prevents the Expression of the Locomotor Sensitization and the Metabolic Changes in the Nucleus Accumbent and Prefrontal Cortex Elicited by the Combined Administration of Cocaine and Caffeine in Rats.

Impact of Plant Density and Irrigation on Yield of Hemp (Cannabis sativa L.) in a Mediterranean Semi-arid Environment

Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors.

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes.

Seeking suitable agronomical practices for industrial hemp (Cannabis sativa L.) cultivation for biomedical applications.

Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes.

Pharmacological potential of varinic-, minor-, and acidic phytocannabinoids

Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors.

The potential of near infrared spectroscopy to estimate the content of cannabinoids in Cannabis sativa L.: A comparative study.

Untargeted characterization of extracts from Cannabis sativa L. cultivars by gas and liquid chromatography coupled to mass spectrometry in high resolution mode.

A Comparative In Vitro Study of the Neuroprotective Effect Induced by Cannabidiol, Cannabigerol, and Their Respective Acid Forms: Relevance of the 5-HT1A Receptors.

Exploring the mysteries of cannabis through gas chromatography

Biological Activity of Cannabis sativa L. Extracts Critically Depends on Solvent Polarity and Decarboxylation.

Thermal desorption-ion mobility spectrometry: A rapid sensor for the detection of cannabinoids and discrimination of Cannabis sativa L. chemotypes

Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors

Politica de Calidad

Ayudas de la Unión Europea para el autoconsumo fotovoltaico

Other services

Plant material

Check our Variety catalogue

Technical assistance

Experience and scientific rigor to walk by your side in your project.

Licensable technology

Use our varieties and patented technological processes.

Research

R+D+i in cultivation, breeding and extraction.

Ask for information

Can we be of help to you? Do you have any questions about us? Write to us and we will contact you as soon as possible.

To enable the functionality of sending messages from the website we need you to accept technical cookies, as we use Google's reCAPTCHA 3 to prevent messages from fraudulent bots.

Accept the use of technical cookies