title: Characterization of cannabinoid receptor ligands in tissues natively expressing cannabinoid CB2 receptors.
abstract: OBJECTIVE
  Although cannabinoid CB₂ receptor ligands have been widely characterized in recombinant systems in vitro, little pharmacological characterization has been performed in tissues natively expressing CB₂ receptors. The aim of this study was to compare the pharmacology of CB₂ receptor ligands in tissue natively expressing CB₂ receptors (human, rat and mouse spleen) and hCB₂-transfected CHO cells.
  
  
  METHODS
  We tested the ability of well-known cannabinoid CB₂ receptor ligands to stimulate or inhibit [³⁵S]GTPγS binding to mouse, rat and human spleen membranes and to hCB₂-transfected CHO cell membranes. cAMP assays were also performed in hCB₂-CHO cells.
  
  
  RESULTS
  The data presented demonstrate that: (i) CP 55,940, WIN 55,212-2 and JWH 133 behave as CB₂ receptor full agonists both in spleen and hCB₂-CHO cells, in both [³⁵S]GTPγS and cAMP assays; (ii) JWH 015 behaves as a low-efficacy agonist in spleen as well as in hCB₂-CHO cells when tested in the [³⁵S]GTPγS assay, while it displays full agonism when tested in the cAMP assay using hCB₂-CHO cells; (iii) (R)-AM 1241 and GW 405833 behave as agonists in the [³⁵S]GTPγS assay using spleen, instead it behaves as a low-efficacy inverse agonist in hCB₂-CHO cells; and (iv) SR 144528, AM 630 and JTE 907 behave as CB₂ receptor inverse agonists in all the tissues.
  
  
  CONCLUSIONS
  Our results demonstrate that CB₂ receptor ligands can display differential pharmacology when assays are conducted in tissues that natively express CB₂ receptors and imply that conclusions from recombinant CB₂ receptors should be treated with caution.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. p.marini@abdn.ac.uk
authors.forename: Pietro
authors.initials: P
authors.lastname: Marini
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Cascio
authors.forename: Angela
authors.initials: A
authors.lastname: King
authors.forename: Roger G
authors.initials: RG
authors.lastname: Pertwee
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Ross
mesh_terms: D000700:Analgesics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D063386:Cannabinoid Receptor Agonists / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D054314:Drug Inverse Agonism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000700:Analgesics; C588309:CNR2 protein, human; D063386:Cannabinoid Receptor Agonists; C571431:Cnr2 protein, mouse; C469526:Cnr2 protein, rat; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP