Abstract

Purpose: Effect of arachidonyl-2-chloroethylamide (ACEA; synthetic cannabinoid receptor agonist) on Angiotensin (Ang) II-induced effects on peroxisome proliferator-activated receptor gamma (PPARg).

Background: Ang II, a peptide of the renin angiotensin system (RAS) activates the NFKB/Cox2/PGE2 inflammatory signaling pathway. There is an interaction between the RAS and the endocannabinoid system. Whether the interaction between the two systems elicits synergistic or antagonist effects on each other requires further studies. Thus, we investigated the role of CB1R agonism on the effects of Ang II on PPARg mRNA expression and the NFKB/Cox2/PGE2 pathway. We previously observed that ACEA activated NFKB but had no effect on Cox2 at 12-24 hours of ACEA treatment. The effect of ACEA treatments on PGE2 levels varied depending on the sample. PPARg was selected as a target because activating this receptor leads to inhibition of NFKB. Understanding the molecular interaction between the two systems may identify potential therapeutic targets to attenuate Ang II effects.

Methods: Quiescent brainstem and cerebellum astrocytes were treated with 10nM ACEA and/or 100nM Ang II for 12-24 hours. PPARg mRNA was determined by quantitative polymerase chain reaction.

Results: Ang II decreased PPARg mRNA in most samples. The decrease was more pronounced in the brainstem compared to the cerebellum astrocytes. ACEA did not significantly alter PPARg mRNA. Treating astrocytes with both Ang II and ACEA did not significantly alter Ang II’s effects.

Conclusions: Given these findings and our previous results, Ang II and ACEA have contrasting effects on the neuroinflammatory pathway examined. ACEA did not appear to alter the Ang II effects examined. ACEA activated the NFKB pathway and decreased PGE2 levels in some samples but had no effect on PPARg and Cox2 at the time intervals examined. Other pathway interactions might account for ACEA effects.