Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor

Gregory I. Liou, John A. Auchampach, Cecilia J. Hillard, Gu Zhu, Bilal Yousufzai, Salman Mian, Sohail Khan, Yousuf Khalifa

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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)-α release in cells or in retinas were determined. RESULTS. The results showed that A2AARs are abundantly expressed in rat retinal microglial cells. When the cells or rats were treated with LPS, activation of the A2AAR was the most efficient in mediating AR agonist- or CBD-induced TNF-α inhibition. CBD inhibited adenosine uptake via equilibrative nucleoside transporter 1 and synergistically enhanced adenosine's TNF-α suppression after treatment with LPS. CONCLUSIONS. These results suggest that the activated A2AAR 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.

Original languageEnglish (US)
Pages (from-to)5526-5531
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number12
DOIs
StatePublished - Dec 1 2008

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Nucleoside Transport Proteins
Cannabidiol
Adenosine A2A Receptors
Adenosine
Retina
Inflammation
Purinergic P1 Receptor Agonists
Lipopolysaccharides
Purinergic P1 Receptors
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Equilibrative Nucleoside Transporter 1
Purinergic P1 Receptor Antagonists
Cannabinoids
Endotoxins
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. / Liou, Gregory I.; Auchampach, John A.; Hillard, Cecilia J.; Zhu, Gu; Yousufzai, Bilal; Mian, Salman; Khan, Sohail; Khalifa, Yousuf.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 12, 01.12.2008, p. 5526-5531.

Research output: Contribution to journalArticle

Liou, Gregory I. ; Auchampach, John A. ; Hillard, Cecilia J. ; Zhu, Gu ; Yousufzai, Bilal ; Mian, Salman ; Khan, Sohail ; Khalifa, Yousuf. / Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 12. pp. 5526-5531.
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N2 - 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)-α release in cells or in retinas were determined. RESULTS. The results showed that A2AARs are abundantly expressed in rat retinal microglial cells. When the cells or rats were treated with LPS, activation of the A2AAR was the most efficient in mediating AR agonist- or CBD-induced TNF-α inhibition. CBD inhibited adenosine uptake via equilibrative nucleoside transporter 1 and synergistically enhanced adenosine's TNF-α suppression after treatment with LPS. CONCLUSIONS. These results suggest that the activated A2AAR 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.

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