ArticleEuropean journal of pharmacology2008
Unique agonist-bound cannabinoid CB1 receptor conformations indicate agonist specificity in signaling.
Article in European journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Plasmon Waveguide Resonance: Principles, Applications and Historical Perspectives on Instrument Development.Molecules (Basel, Switzerland) · 2021Review
- Structural Insights into CB1 Receptor Biased Signaling.International journal of molecular sciences · 2019Review
- Tolerance to WIN55,212-2 is delayed in desensitization-resistant S426A/S430A mice.Neuropharmacology · 2019Article
- Improved Detection of Plasmon Waveguide Resonance Using Diverging Beam, Liquid Crystal Retarder, and Application to Lipid Orientation Determination.Sensors (Basel, Switzerland) · 2019Article
- Atypical Endocannabinoid Signaling Initiates a New Form of Memory-Related Plasticity at a Cortical Input to Hippocampus.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Cannabigerol Action at Cannabinoid CBFrontiers in pharmacology · 2018Article
- The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors.Nature communications · 2017Article
- Ligand activation induces different conformational changes in CXCR3 receptor isoforms as evidenced by plasmon waveguide resonance (PWR).Scientific reports · 2017Article
- CBAdvances in pharmacology (San Diego, Calif.) · 2017Review
- Cannabinoid CBCannabis and cannabinoid research · 2017Review
- Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons.The Journal of biological chemistry · 2014Article
- Signalling bias in new drug discovery: detection, quantification and therapeutic impact.Nature reviews. Drug discovery · 2013Review
- CB(1) receptor allosteric modulators display both agonist and signaling pathway specificity.Molecular pharmacology · 2013Article
- New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2.British journal of pharmacology · 2013Review
- Article
- The potential for selective pharmacological therapies through biased receptor signaling.BMC pharmacology & toxicology · 2012Review
- Probing heterotrimeric G protein activation: applications to biased ligands.Current pharmaceutical design · 2012Review
- Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors.Annual review of pharmacology and toxicology · 2012Review
- The significance of G protein-coupled receptor crystallography for drug discovery.Pharmacological reviews · 2011Review
- Dual neuroprotective and neurotoxic effects of cannabinoid drugs in vitro.Cellular and molecular neurobiology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Cannabinoid drugs differ in their rank order of potency to produce analgesia versus other central nervous system effects. We propose that these differences are due to unique agonist-bound cannabinoid CB1 receptor conformations that exhibit different affinities for individual subsets of intracellular signal transduction pathways. In order to test this hypothesis, we have used plasmon-waveguide resonance (PWR) spectroscopy, a sensitive method that can provide direct information about ligand-protein and protein-protein interactions, and can detect conformational changes in lipid-embedded proteins. A recombinant epitope-tagged human cannabinoid CB1 receptor was expressed in insect Sf9 cells, solubilized and purified using two-step affinity chromatography. The purified receptor was incorporated into a lipid bilayer on the surface of the PWR resonator. PWR spectroscopy demonstrated that cannabinoid agonists exhibit high affinity (KD=0.2+/-0.03 nM and 2+/-0.4 nM for CP 55,940 and WIN 55,212-2, respectively) for the purified epitope tagged hCB(1) receptor. Interestingly however, these structurally different cannabinoid agonists shifted the PWR spectra in opposite directions, indicating that CP 55,940 and WIN 55,212-2 binding leads to different hCB1 receptor conformations. Furthermore, PWR experiments also indicated that these CP 55,940-and WIN 55,212-bound hCB1 receptor conformations exhibit slightly different affinities to an inhibitory G protein heterotrimer, Gi1 (KD=27+/-8 nM and KD=10.7+/-4.7 nM, respectively), whereas they strikingly differ in their ability to activate this G protein type.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.