The enigmatic pharmacology of GPR55.
Preliminary data presented at conferences and in the patent literature introduced the possibility the orphan receptor GPR55 might account for some of the well-documented non-CB(1), non-CB(2) effects reported for certain cannabinoid ligands. Several peer-reviewed publications have recently emerged in which the pharmacology of the cannabinoids at GPR55 has been probed in more depth. Despite this, the classification of GPR55 as a cannabinoid receptor remains a contentious issue. The weight of evidence points to GPR55 as a receptor that is activated by certain cannabinoid ligands and by the bioactive lipid l-alpha-lysophosphatidylinsoitol. It couples to G(12) proteins, activates RhoA and mobilizes intracellular Ca(2+), possibly in an agonist- and tissue-dependant manner, thus displaying 'agonist functional selectivity'. Here, I review the recent literature in an effort to glean the key controversies and outstanding questions surrounding the interaction between cannabinoids and this orphan receptor.
Ross
Ruth A
RA
Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, Scotland, UK. r.ross@abdn.ac.uk
D000818:Animals; D001665:Binding Sites; D063386:Cannabinoid Receptor Agonists; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism* / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism* / Q000494:pharmacology; D008024:Ligands; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D043882:Receptors, Cannabinoid / Q000145:classification / Q000502:physiology*; D049312:Receptors, Lysophospholipid / Q000819:agonists / Q000145:classification / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D063386:Cannabinoid Receptor Agonists; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; C526692:GPR55 protein, mouse; D008024:Ligands; D008246:Lysophospholipids; D043882:Receptors, Cannabinoid; D049312:Receptors, Lysophospholipid; C025449:lysophosphatidylinositol