CONICET | Buscador de Institutos y Recursos Humanos

Endogenous cannabinoids are an emerging class of lipid mediators found in both brain and peripheral tissues and activate type 1 and type 2 cannabinoid receptros (CB1 and CB2) These receptors also bind the psychoactive component of marijuana. Two arachidontate dereivates, N.arachidonoylethanolamine (anandamide, AAEA) and 2-arachidonoylglycerol (2-AG) are the endocannabinopids whose biological activity has best been characterized to date. Anandamide was the first eCB isolated from brain tissue. It is released from a cell membrane phospholipid precursor (NAPE) in response to depolarizing agents, hormones and neurotransmitters in part via NAPE-specific phospholipase D (PLD). The levels of AEA appear to be controlled by its cellular uptake through a putative eCB membrane transporter and its subsequent enzymatic degradation into arachidonic acid and ethanolamine by a membrane bound fatty acid amide hydrolase (FAAH). AEA effects are determined by its interaction with both CB1 and CB2 receptors belonging to the superfamily of G protein-coupled receptors. CB1 is most abundant in the central nervous system but it is also present in peripheral tissues including the heart, uterus, ovary, testis, placenta, liver and small intestine. CB2 is predominantly expressed in glia, spleen and immune cells. Furthermore, transient receptors potential vanilloid 1 (TRPV1) channels also is activated by eCBs. Endocannabinoids biological actions are controlled through not yet fully characterized cellular mechanisms. These compounds, together with their related enzymes, that include key proteins for the synthesis and degradation of endocannabinoids, cannabinoid and non-cannabinoid receptors, and membrane transporters, form the "endocannabinoid system (ECS)". In the past few years AEA and related ECS elements have emerged as essential players in various aspects of human reproduction, both of males and females. Most of human reproductive cells and tissues, such as blatocysts, spermatozoa, uterus and testis, posses the biochemical machinery to synthesize and degrade eCB. Interestingly, several studies have highlighted the therapeutic potential of FAAH as a "checkpoint" in the regulation of EA tone and signaling in human reproduction, focusing attention on its interaction with hormones, cytokines and other mediators involved in the multifaceted process of procreation.