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The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55.
J Neuroimmune Pharmacol 2012; 7(4):856-65JN

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 β-arrestin2 (βarr2) 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 βarr2. 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.

Authors+Show Affiliations

Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22454039

Citation

Sharir, Haleli, et al. "The Endocannabinoids Anandamide and Virodhamine Modulate the Activity of the Candidate Cannabinoid Receptor GPR55." Journal of Neuroimmune Pharmacology : the Official Journal of the Society On NeuroImmune Pharmacology, vol. 7, no. 4, 2012, pp. 856-65.
Sharir H, Console-Bram L, Mundy C, et al. The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. J Neuroimmune Pharmacol. 2012;7(4):856-65.
Sharir, H., Console-Bram, L., Mundy, C., Popoff, S. N., Kapur, A., & Abood, M. E. (2012). The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. Journal of Neuroimmune Pharmacology : the Official Journal of the Society On NeuroImmune Pharmacology, 7(4), pp. 856-65. doi:10.1007/s11481-012-9351-6.
Sharir H, et al. The Endocannabinoids Anandamide and Virodhamine Modulate the Activity of the Candidate Cannabinoid Receptor GPR55. J Neuroimmune Pharmacol. 2012;7(4):856-65. PubMed PMID: 22454039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. AU - Sharir,Haleli, AU - Console-Bram,Linda, AU - Mundy,Christina, AU - Popoff,Steven N, AU - Kapur,Ankur, AU - Abood,Mary E, Y1 - 2012/03/28/ PY - 2011/10/26/received PY - 2012/02/21/accepted PY - 2012/3/29/entrez PY - 2012/3/29/pubmed PY - 2013/5/28/medline SP - 856 EP - 65 JF - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JO - J Neuroimmune Pharmacol VL - 7 IS - 4 N2 - 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 β-arrestin2 (βarr2) 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 βarr2. 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. SN - 1557-1904 UR - https://www.unboundmedicine.com/medline/citation/22454039/The_endocannabinoids_anandamide_and_virodhamine_modulate_the_activity_of_the_candidate_cannabinoid_receptor_GPR55_ L2 - https://doi.org/10.1007/s11481-012-9351-6 DB - PRIME DP - Unbound Medicine ER -