The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55.
J Neuroimmune Pharmacol
; 7(4): 856-65, 2012 Dec.
Article
in En
| MEDLINE
| ID: mdl-22454039
ABSTRACT
The role of cannabinoid receptors in inflammation has been the topic of many research endeavors. Despite this effort, to date the involvement of the endocannabinoid system (ECS) in inflammation remains obscure. The ambiguity of cannabinoid involvement may be explained by the existence of cannabinoid receptors, other than CB(1) and CB(2), or a consequence of interaction of endocannabinoids with other signaling systems. GPR55 has been proposed to be a cannabinoid receptor; however the interaction of the endocannabinoid system with GPR55 remains elusive. Consequently this study set about to examine the effects of the endocannabinoids, anandamide (AEA) and virodhamine, on GPR55 mediated signaling. Specifically, we assessed changes in ß-arrestin2 (ßarr2) distribution and GPR55 receptor internalization following activation by lysophosphatidylinositol (LPI), the synthetic cannabinoid ligand SR141716A, and new selective synthetic GPR55 agonists. Data obtained from the experiments presented herein demonstrate that AEA and virodhamine modulate agonist-mediated recruitment of ßarr2. AEA and virodhamine act as partial agonists; enhancing the agonist effect at low concentrations and inhibiting it at high concentrations. Furthermore, both virodhamine and AEA significantly attenuated agonist-induced internalization of GPR55. These effects are attributed to the expression of GPR55, and not CB(1) and CB(2) receptors, as we have established negligible expression of CB(1) and CB(2) in these GPR55-transfected U2OS cells. The identification of select endocannabinoids as GPR55 modulators will aide in elucidating the function of GPR55 in the ECS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cannabinoids
/
Arachidonic Acids
/
Receptors, G-Protein-Coupled
/
Endocannabinoids
/
Polyunsaturated Alkamides
/
Cannabinoid Receptor Modulators
/
Cannabinoid Receptor Agonists
Limits:
Animals
/
Humans
Language:
En
Journal:
J Neuroimmune Pharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
NEUROLOGIA
Year:
2012
Document type:
Article
Affiliation country:
United States