Aspirin-triggered lipoxin induces CB1-dependent catalepsy in mice

NEUROSCIENCE LETTERS

卷:470

Article

Pamplona, Fabricio A.¹  Menezes-de-Lima, Octavio, Jr.²  Takahashi, Reinaldo N.¹ 

[1] Univ Fed Santa Catarina, Dept Farmacol, CCB, BR-88049900 Florianopolis, SC, Brazil

[2] Fiocruz MS, Lab Farmacol Aplicada, BR-21045900 Rio De Janeiro, Brazil

关键词: Aspirin-triggered lipoxin;    15-Epi-lipoxin A(4);    Endocannabinoid;    Anandamide;    Lipoxygenase;   

DOI  :  10.1016/j.neulet.2009.12.050

来源: Elsevier

【 摘 要 】

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 A(4) (15-epi-LXA(4)), an aspirin-triggered lipoxin. Our objective was to investigate whether 15-epi-LXA(4) 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 close-dependent (200 pmol/2 mu l, i.c.v.) catalepsy. A sub-dose of AEA (110 pmol/2 mu l, 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 1 5-epi-LXA(4) (0.01 pmol/2 mu l, i.c.v.) and AEA (10 pmol/2 mu l, 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 mu g/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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free