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 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 in the presence or absence of adenosine, adenosine receptor agonists/antagonists, or CBD. Adenosine uptake and tumor necrosis factor-α release in cells or in retinas were determined.
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.
Drugs that enhance extracellular adenosine signaling have been of clinical interest in treatment of inflammation after myocardial or cerebral ischemia
CBD as an anti-inflammatory drug is an attractive alternative to smoking marijuana because of its lack of psychoactive effects.CBD is known to be nontoxic in humans, 28 which has previously been a problem for other nucleoside inhibitor drugs.Another potential problem with chronic consumption of adenosine transporter inhibitor is the development of tolerance due to cell tolerance of adenosine through receptor desensitization. It is important to determine the long-term effects of CBD use on adenosine receptors.z7g01208005526