Gαs signalling of the CB1 receptor and the influence of receptor number.

British Journal of Pharmacology
David B FinlayM Glass

Abstract

CB1 receptor signalling is canonically mediated through inhibitory Gαi proteins, but occurs through other G proteins under some circumstances, Gαs being the most characterized secondary pathway. Determinants of this signalling switch identified to date include Gαi blockade, CB1 /D2 receptor co-stimulation, CB1 agonist class and cell background. Hence, we examined the effects of receptor number and different ligands on CB1 receptor signalling. CB1 receptors were expressed in HEK cells at different levels, and signalling characterized for cAMP by real-time BRET biosensor -CAMYEL - and for phospho-ERK by AlphaScreen. Homogenate and whole cell radioligand binding assays were performed to characterize AM6544, a novel irreversible CB1 receptor antagonist. In HEK cells expressing high levels of CB1 receptors, agonist treatment stimulated cAMP, a response not known to be mediated by receptor number. Δ9 -THC and BAY59-3074 increased cAMP only in high-expressing cells pretreated with pertussis toxin, and agonists demonstrated more diverse signalling profiles in the stimulatory pathway than the canonical inhibitory pathway. Pharmacological CB1 receptor knockdown and Gαi 1 supplementation restored canonical Gαi signalling to high-expressin...Continue Reading

References

Dec 22, 1983·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·J W Black, P Leff
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·K L LaugwitzG Schultz
Oct 15, 1998·FEBS Letters·C SánchezM Guzmán
Dec 24, 1998·British Journal of Pharmacology·R A RossR G Pertwee
Sep 7, 2001·Biochemical Pharmacology·J NasmanK E Akerman
Mar 21, 2002·The Biochemical Journal·Teresa Gómez del PulgarManuel Guzmán
Nov 25, 2003·The Journal of Pharmacology and Experimental Therapeutics·A JarrahianE L Barker
Mar 8, 2005·Molecular Pharmacology·Somnath Mukhopadhyay, Allyn C Howlett
Apr 5, 2005·The Journal of Pharmacology and Experimental Therapeutics·Stuart MaudsleyLouis M Luttrell
Aug 9, 2005·The Journal of Peptide Research : Official Journal of the American Peptide Society·W XuA Makriyannis
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jane E LaucknerKen Mackie
Jun 29, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jonathan D UrbanRichard B Mailman
Feb 7, 2007·The Journal of Biological Chemistry·Lily I JiangPaul C Sternweis
Oct 9, 2007·British Journal of Pharmacology·B T McIntoshM E M Kelly
Dec 6, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sui Chu ChungChristopher J Fowler
May 9, 2009·The Journal of Clinical Investigation·María SalazarGuillermo Velasco
Dec 18, 2009·The Journal of Pharmacology and Experimental Therapeutics·Julie A Przybyla, Val J Watts
Jul 2, 2010·British Journal of Pharmacology·E L ScotterM Glass
Oct 28, 2010·British Journal of Pharmacology·David A Hall, Christopher J Langmead
Jun 7, 2011·Biochimica Et Biophysica Acta·Natasha L GrimseyMichelle Glass
Aug 4, 2012·ACS Chemical Neuroscience·Terry KenakinSteven Novick
Jun 12, 2013·PloS One·Mariateresa CiprianoChristopher J Fowler
Dec 19, 2013·PloS One·Alexander H BenzFaramarz Dehghani
Apr 12, 2014·American Journal of Obstetrics and Gynecology·Enrico Michelino MessalliRaffaele Rossiello
Feb 24, 2015·Trends in Pharmacological Sciences·Sergi Ferré
Jun 15, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Guillermo VelascoMar Lorente
Jun 27, 2015·British Journal of Pharmacology·Michael J CurtisJohn C McGrath
Dec 10, 2015·British Journal of Pharmacology·Stephen Ph AlexanderCgtp Collaborators

❮ Previous
Next ❯

Citations

Aug 31, 2018·Minerva ginecologica·Laura RiccettiManuela Simoni
Apr 25, 2019·International Journal of Molecular Sciences·Rufaida Al-ZoubiPatricia H Reggio
Oct 15, 2019·Synapse·Gabriel López-RamírezBenjamín Florán
Aug 15, 2019·British Journal of Pharmacology·Shivani SachdevMark Connor
Feb 27, 2020·Pharmacology Research & Perspectives·Shivani SachdevMark Connor
Apr 16, 2020·British Journal of Pharmacology·Xiao ZhuStephen B Duffull
Jul 11, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·João MaiaGeorgina Correia-da-Silva
Apr 27, 2019·Frontiers in Pharmacology·Mikkel Søes IbsenNatasha Lillia Grimsey
Jun 14, 2019·Frontiers in Pharmacology·Richard C KevinSamuel D Banister
Apr 27, 2019·Frontiers in Pharmacology·UNKNOWN Frontiers Production Office
Aug 29, 2020·International Journal of Molecular Sciences·Kenneth B Walsh, Haley K Andersen
Dec 14, 2018·Frontiers in Pharmacology·Caitlin R M OyagawaNatasha Lillia Grimsey
Apr 10, 2020·Frontiers in Pharmacology·David B FinlayMichelle Glass
Nov 5, 2020·Cell Chemical Biology·Aurélien LaguerreCarsten Schultz
Nov 5, 2020·International Journal of Molecular Sciences·Paula MoralesM Angeles Jiménez
Jun 14, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gerwyn MorrisAndre F Carvalho
Jul 22, 2021·Biochemistry. Biokhimii︠a︡·Olga P BalezinaAlexander E Gaydukov
Apr 8, 2020·ACS Pharmacology & Translational Science·Yurii SarozNatasha Lillia Grimsey
Apr 17, 2020·ACS Pharmacology & Translational Science·Elise WoutersChristophe Stove
Nov 9, 2021·Frontiers in Endocrinology·Viktória B HorváthGergő Szanda

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biosensors for Cancer Detection

Biosensors are devices that are designed to detect a specific biological analyte by essentially converting a biological entity (ie, protein, DNA, RNA) into an electrical signal that can be detected and analyzed. The use of biosensors in cancer detection and monitoring holds vast potential. Biosensors can be designed to detect emerging cancer biomarkers and to determine drug effectiveness at various target sites. Biosensor technology has the potential to provide fast and accurate detection, reliable imaging of cancer cells, and monitoring of angiogenesis and cancer metastasis, and the ability to determine the effectiveness of anticancer chemotherapy agents.