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Akhilesh Kumar, Zhuanhong Qiao, Pritesh Kumar, Zhao-Hui Song; Effect of Palmitylethanolamide on Aqueous Humor Outflow. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1524.
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To study the effects of palmitoylethanolamide (PEA), a fatty acid ethanolamide and an endogenous cannabinoid, on aqueous humor outflow via the trabecular meshwork pathway.
The effects of PEA on aqueous humor outflow via the trabecular meshwork pathway were measured using a porcine anterior segment perfused organ culture model. Different concentrations of PEA were administered to the perfusion medium and the aqueous humor outflow facility was monitored for 5 hours. CB1 antagonist SR141716A and CB2 antagonist SR144528 were used, respectively, to investigate the possible involvement of CB1 and CB2 receptors in the outflow effects induced by PEA. O-1918, a cannabidiol analog that acts as a selective antagonist at the non-CB1/CB2 receptors, was also used to investigate whether non-CB1/CB2 cannabinoid receptors are involved in the PEA-induced outflow effects. PEA induced activation of p42/44 mitogen-activated protein (MAP) kinase was determined by western blot analysis using an anti-phospho p42/44 MAP kinase antibody.
Administration of PEA caused a concentration-dependent enhancement of aqueous humor outflow facility, with the maximum effect (135.6 ± 7.1 % of basal outflow facility) achieved at 2 hour after the administration of 30 nM of PEA. Pretreatment with 1 µM O-1918 produced a full antagonism on the PEA-induced increase of aqueous humor outflow facility. However, pretreatment with 1µM of SR141716A or 1µM of SR141716A had no effect on PEA-induced enhancement of aqueous humor outflow facility. Treatment of trabecular meshwork cells with PEA for 10 min activated phosphorylation of p42/44 MAP kinase which was blocked by pretreatment with O-1918. Furthermore, PD98059, an inhibitor of the p42/44 MAP kinase pathway, blocked both PEA-induced phosphorylation of p42/44 MAP kinase and enhancement of aqueous humor outflow facility.
The results from this study demonstrate that PEA increases aqueous humor outflow through the trabecular meshwork pathway, and these effects are mediated by non-CB1/CB2 cannabinoid receptors through activation of p42/44.
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