Conference name: 15th Scientific Symposium of the Austrian Pharmacological Society (APHAR) Joint meeting with the Hungarian Society of Experimental and Clinical Pharmacology (MFT) and the Slovenian Pharmacological Society (SDF)
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Abstract
Background
CB1 and CB2 cannabinoid receptors are G protein-coupled receptors which have been
described to couple mainly to the Gi/o subfamily of G proteins. However, in some cell
types and upon stimulation with certain cannabinoid agonists, activation of other
G protein subtypes has also been observed. GPR55 is an orphan G protein-coupled receptor
which has been suggested to be a novel member of the cannabinoid receptor family.
Methods
In this study we wanted to characterize the G protein activation properties of the
two known cannabinoid receptors and GPR55 following stimulation with different cannabinoid
ligands, using bioluminescence resonance energy transfer (BRET). We monitored the
activation of different G protein subtypes (Go, Gq, Gs or G12) using Renilla luciferase-tagged
wild type or chimeric Gαo subunits (i.e. Gαo with the C-terminal 5 amino acids replaced
with those of Gαq, Gαs or Gα12, respectively) co-expressed with EYFP-tagged α1α11
subunit and the receptor in CHO cells.
Results
We found that CB1 was able to activate all four subtypes of G proteins, with different
pharmacokinetic properties, following stimulation by non-selective (WIN55 and 2-AG)
or CB1-selective (ACEA) cannabinoid agonists. Basal activity of CB1 could also be
detected with Go and G12 subtypes, as the CB1 inverse agonist AM251 caused significant
BRET increase (i.e. G protein subunit association) when tested with these G proteins.
In contrast, CB2 showed no G protein activation other than Go, upon either WIN55 or
2-AG stimuli. Stimulation of GPR55 with WIN55, 2-AG or AM251 did not alter the activity
of the tested G proteins even at considerably high ligand concentrations.
Conference name:
15th Scientific Symposium of the Austrian Pharmacological Society (APHAR) Joint meeting
with the Hungarian Society of Experimental and Clinical Pharmacology (MFT) and the
Slovenian Pharmacological Society (SDF)