Abstract

Anandamide, an endocannabinoid, prostaglandins derived from cyclooxygenase-2 and nitric oxide synthesized by nitric oxide synthase (NOS), are relevant mediators of embryo implantation. We adopted a pharmacological approach to investigate if anandamide modulated NOS activity in the receptive rat uterus and if prostaglandins mediated this effect. As we were interested in studying the changes that occur at the maternal side of the fetal-maternal interface, we worked with uteri obtained from pseudopregnant rats. Females were sacrificed on day 5 of pseudopregnancy, the day in which implantation would occur, and the uterus was obtained. Anandamide (2 ng/kg, i.p.) inhibited NOS activity (P<0.001) and increased the levels of prostaglandin E(2) (P<0.001) and prostaglandin F(2α) (P<0.01). These effects were mediated via cannabinoid receptor type 2, 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 a non-selective cyclooxygenase inhibitor (indomethacin 2.5mg/kg, i.p.) or with selective cyclooxygenase-2 inhibitors (meloxicam 4 mg/kg, celecoxib 3mg/kg, i.p.) reverted anandamide inhibition on NOS, suggesting that prostaglandins are derived from cyclooxygenase-2 mediated anandamide effect. Thus, anandamide levels 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 the treatment of implantation deficiencies.

Links

Publisher Full Text

Authors

Sordelli MS, Beltrame JS, Cella M, Franchi AM, Ribeiro ML

Institution

Laboratorio de Fisiología y Farmacología de Reproducción, CEFYBO (CONICET-UBA), Paraguay 2155, 16th floor, CP (C1121ABG), Buenos Aires, Argentina.

Source

European journal of pharmacology 685:1-3 2012 Jun 15 pg 174-9

MeSH

Animals
Arachidonic Acids
Bornanes
Cyclooxygenase 2
Cyclooxygenase Inhibitors
Dinoprost
Dinoprostone
Endocannabinoids
Female
Nitric Oxide Synthase
Polyunsaturated Alkamides
Pseudopregnancy
Pyrazoles
Rats
Rats, Wistar
Receptor, Cannabinoid, CB2
Uterus

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22554772