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

European Journal of Pharmacology
Micaela S SordelliM L Ribeiro

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 inhibit...Continue Reading

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Citations

Jun 8, 2013·Reproduction : the Official Journal of the Society for the Study of Fertility·Hsiu-Wen ChanMurray D Mitchell
Nov 15, 2013·International Journal of Endocrinology·B M FonsecaN A Teixeira
May 24, 2014·The Journal of Nutritional Biochemistry·Jeffrey Kim, Bruce A Watkins
Nov 1, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Fernando CorreaAna María Franchi
Apr 29, 2015·Experimental Animals·Lu YangChengzhi Chai
Feb 22, 2017·Apoptosis : an International Journal on Programmed Cell Death·M AlmadaN Teixeira
Nov 5, 2020·Animals : an Open Access Journal From MDPI·Roberto Rodrigues da Rosa FilhoCamila Infantosi Vannucchi
Jun 8, 2021·Frontiers in Physiology·Paula AccialiniMariana Farina
Jul 3, 2021·International Journal of Molecular Sciences·Laura BarberioMaurizio Mandalà

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