Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. Invest Ophthalmol Vis Sci 2008 Dec;49(12):5526-31
Date
07/22/2008Pubmed ID
18641283Pubmed Central ID
PMC2588644DOI
10.1167/iovs.08-2196Scopus ID
2-s2.0-58149269741 (requires institutional sign-in at Scopus site) 119 CitationsAbstract
PURPOSE: Cannabidiol (CBD), a nonpsychotropic, nontoxic compound has been shown to block diabetes- and endotoxin-induced retinal damage. However, the protective mechanism of this anti-inflammatory cannabinoid is not completely understood. The goal of this study is to determine the role of adenosine signaling in retinal inflammation and its potential modulation by CBD.
METHODS: The adenosine receptor (AR) subtypes expressed in rat retinal microglial cells were assessed by quantitative real-time RT-PCR. AR function was determined via in vitro and in vivo inflammatory models. Microglial cells or rats were treated with or without lipopolysaccharide (LPS) in the presence or absence of adenosine, adenosine receptor agonists/antagonists, or CBD. Adenosine uptake and tumor necrosis factor (TNF)-alpha release in cells or in retinas were determined.
RESULTS: The results showed that A(2A)ARs are abundantly expressed in rat retinal microglial cells. When the cells or rats were treated with LPS, activation of the A(2A)AR was the most efficient in mediating AR agonist- or CBD-induced TNF-alpha inhibition. CBD inhibited adenosine uptake via equilibrative nucleoside transporter 1 and synergistically enhanced adenosine's TNF-alpha suppression after treatment with LPS.
CONCLUSIONS: These results suggest that the activated A(2A)AR in the retinal microglial cells plays a major anti-inflammatory role in the retina and that CBD's anti-inflammatory effects are linked to the inhibition of adenosine uptake.
Author List
Liou GI, Auchampach JA, Hillard CJ, Zhu G, Yousufzai B, Mian S, Khan S, Khalifa YAuthors
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinCecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adenosine A2 Receptor AgonistsAdenosine A2 Receptor Antagonists
Animals
Anti-Inflammatory Agents
Cannabidiol
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Lipopolysaccharides
Male
Microglia
Nucleoside Transport Proteins
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A2A
Retina
Reverse Transcriptase Polymerase Chain Reaction
Salmonella enterica
Tumor Necrosis Factor-alpha
