The endocannabinoid system functions through two well characterized receptor systems termed CB<sub>1</sub> and CB<sub>2</sub>. However a growing body of evidence exists that suggest that the system is more complicated and indicate the presence of additional receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological activities. In this thesis it is demonstrated that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GPR55 with nM potencies. Ligands having no CB<sub>1</sub> or CB<sub>2</sub> activity that are believed to function at some of these novel receptor types such as cannabidiol and abnormal cannabidiol effect activity of GPR55. These data suggest that GRP55 is a novel cannabinoid receptor, and its relative preference for ligands with respect to CB<sub>1 </sub>and CB<sub>2</sub> described here will permit delineation of its physiological function. Data also suggesting that GRP55 couples to Gα13 and can mediate activation of RhoA, rac1 and cdc42. It’s also demonstrated that GPR55 is functionally expressed in the mouse brain and using CB<sub>1</sub> and GPR55 selective ligands it is possible to functionally distinguish these receptors. It is therefore probable that both these receptors contribute to cannabinoid activity in CNS function.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:521231 |
| Date | January 2009 |
| Creators | Ryberg, Erik |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=61555 |
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