Aspirin-triggered lipoxin induces CB1-dependent catalepsy in mice.
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 dose-dependent (200 pmol/2 microl, i.c.v.) catalepsy. A sub-dose of AEA (10 pmol/2 microl, 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-LXA(4) (0.01 pmol/2 microl, i.c.v.) and AEA (10 pmol/2 microl, i.c.v.) was prevented by the cannabinoid CB(1) receptors antagonist SR141716A (1mg/kg, i.p.), but not by the antagonist of lipoxin ALX receptors Boc-2 (10 microg/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.
Pamplona
Fabrício A
FA
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Menezes-de-Lima
Octávio
O
Takahashi
Reinaldo N
RN
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D063388:Endocannabinoids; D044045:Lipoxins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008959:Models, Neurological; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant
D001095:Arachidonic Acids; D002491:Central Nervous System Agents; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D044045:Lipoxins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D044067:Receptors, Lipoxin; C040527:lipoxin A4; D001094:Arachidonate 5-Lipoxygenase; D001241:Aspirin; D000077285:Rimonabant; C078814:anandamide