Cyclooxygenase-2 prostaglandins mediate anandamide-inhibitory action on nitric oxide synthase activity in the receptive rat uterus

SORDELLI, MICAELA SOLEDAD; BELTRAME JIMENA; CELLA, MAXIMILIANO; FRANCHI, ANA MARIA; RIBEIRO MARIA LAURA

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 vol. 685 p. 174 - 179

0014-2999

Anandamide, an endocannabinoid, prostaglandins derived from cyclooxygenase-2 and nitric oxide synthesizedby nitric oxide synthase (NOS), are relevant mediators of embryo implantation. We adopted a pharmacologicalapproach to investigate if anandamide modulated NOS activity in the receptive rat uterus and ifprostaglandins mediated this effect. As we were interested in studying the changes that occur at the maternalside of the fetal–maternal interface, we worked with uteri obtained from pseudopregnant rats. Females weresacrificed on day 5 of pseudopregnancy, the day in which implantation would occur, and the uterus wasobtained. Anandamide (2 ng/kg, i.p.) inhibited NOS activity (Pb0.001) and increased the levels of prostaglandinE2 (Pb0.001) and prostaglandin F2α (Pb0.01). These effects were mediated via cannabinoid receptor type2, as the pre-treatment with SR144528 (10 mg/kg, i.p.), a selective cannabinoid receptor type 2 antagonist,completely reverted anandamide effect on NOS activity and prostaglandin levels. The pre-treatment with anon-selective cyclooxygenase inhibitor (indomethacin 2.5 mg/kg, i.p.) or with selective cyclooxygenase-2 inhibitors(meloxicam 4 mg/kg, celecoxib 3 mg/kg, i.p.) reverted anandamide inhibition on NOS, suggestingthat prostaglandins are derived from cyclooxygenase-2 mediated anandamide effect. Thus, anandamidelevels seemed to modulate NOS activity, fundamental for implantation, via cannabinoid receptor type 2 receptors,in the receptive uterus. This modulation depends on the production of cyclooxygenase-2 derivatives.These data establish cannabinoid receptors and cyclooxygenase enzymes as an interesting target for thetreatment of implantation deficiencies.