کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4346544 | 1296793 | 2010 | 5 صفحه PDF | دانلود رایگان |

Evidence are that inhibition of cyclooxygenase 2 (COX-2) enhances endocannabinoid signaling, indicating a crosstalk between these two eicosanoid pathways. Aspirin, a non-selective COX inhibitor, acetylates COX-2 with generation of a lipoxygenase (LOX) substrate, whose end product is the 15-epi-lipoxin A4 (15-epi-LXA4), an aspirin-triggered lipoxin. Our objective was to investigate whether 15-epi-LXA4 would potentiate in vivo effects of the endocannabinoid anandamide (AEA). Catalepsy was selected as a behavioral parameter and tested 5 min after AEA injection in all experiments. AEA induced dose-dependent (200 pmol/2 μl, i.c.v.) catalepsy. A sub-dose of AEA (10 pmol/2 μl, i.c.v.) was potentiated by aspirin (300 mg/kg, p.o.) via a 5-LOX-dependent step. The cataleptic effect induced by the interaction between sub-doses of 15-epi-LXA4 (0.01 pmol/2 μl, i.c.v.) and AEA (10 pmol/2 μl, i.c.v.) was prevented by the cannabinoid CB1 receptors antagonist SR141716A (1 mg/kg, i.p.), but not by the antagonist of lipoxin ALX receptors Boc-2 (10 μg/kg, i.p.). While previous studies have shown that COX inhibition itself may enhance endocannabinoid effects, here we add another piece of evidence revealing that a LOX-derivative produced in consequence of COX-2 acetylation participates in this process.
Journal: Neuroscience Letters - Volume 470, Issue 1, 5 February 2010, Pages 33–37