Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB


Journal

Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422

Informations de publication

Date de publication:
09 2020
Historique:
received: 19 04 2020
revised: 13 05 2020
accepted: 15 05 2020
pubmed: 30 5 2020
medline: 7 7 2021
entrez: 30 5 2020
Statut: ppublish

Résumé

Recent approved medicines whose active principles are Δ Cannabinoid CB Determination of the affinity of phytocannabinoids for cannabinoid receptors and functional assessment of effects promoted by these compounds when interacting with cannabinoid receptors. A heterologous system expressing the human versions of CB 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. Results here reported and the recent elucidation of the three-dimensional structure of CB

Sections du résumé

BACKGROUND
Recent approved medicines whose active principles are Δ
HYPOTHESIS/PURPOSE
Cannabinoid CB
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 CB
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 CB

Identifiants

pubmed: 32470563
pii: S1043-6618(20)31248-2
doi: 10.1016/j.phrs.2020.104940
pii:
doi:

Substances chimiques

CNR1 protein, human 0
CNR2 protein, human 0
Cannabinoids 0
Ligands 0
Receptor, Cannabinoid, CB1 0
Receptor, Cannabinoid, CB2 0
beta-Arrestins 0
Cannabidiol 19GBJ60SN5
Cyclic AMP E0399OZS9N
Extracellular Signal-Regulated MAP Kinases EC 2.7.11.24
cannabigerol J1K406072N

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104940

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Gemma Navarro (G)

Department of Biochemistry and Physiology. School of Pharmacy and Food Sciences, Universitat de Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CiberNed), Spain.

Katia Varani (K)

Department of Morphology, Surgery and Experimental Medicine, Ferrara University, Ferrara, Italy.

Alejandro Lillo (A)

Department of Biochemistry and Physiology. School of Pharmacy and Food Sciences, Universitat de Barcelona, Spain; Department of Biochemistry and Molecular Biomedicine. Universitat de Barcelona, Spain.

Fabrizio Vincenzi (F)

Department of Morphology, Surgery and Experimental Medicine, Ferrara University, Ferrara, Italy.

Rafael Rivas-Santisteban (R)

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CiberNed), Spain; Department of Biochemistry and Molecular Biomedicine. Universitat de Barcelona, Spain.

Iu Raïch (I)

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CiberNed), Spain; Department of Biochemistry and Molecular Biomedicine. Universitat de Barcelona, Spain.

Irene Reyes-Resina (I)

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CiberNed), Spain; Department of Biochemistry and Molecular Biomedicine. Universitat de Barcelona, Spain.

Carlos Ferreiro-Vera (C)

Phytoplant Research S.L., Córdoba, Spain.

Pier Andrea Borea (PA)

Ferrara University, Ferrara, Italy.

Verónica Sánchez de Medina (V)

Phytoplant Research S.L., Córdoba, Spain.

Xavier Nadal (X)

Independent Researcher, Córdoba, Spain.

Rafael Franco (R)

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CiberNed), Spain; Department of Biochemistry and Molecular Biomedicine. Universitat de Barcelona, Spain. Electronic address: rfranco@ub.edu.

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Classifications MeSH