while PGs metabolised by COX 2 are involved in inflammation, ovulation and mitogenesis. COX 1 is a constitutive enzyme found in the cell new membranes of most mammalian tissues, while COX 2 is an inducible enzyme, not found in all cell types, that is located in nuclear membranes. In the mammalian LOX pathway AA is converted by different LOXs into hydroperoxyeicosatetraenoic acids that may be further metabolised into hydroxyeicosatetraenoic acids by glutathione peroxidase. Leukotrienes are syn thesised from 5 HPETE by 5 LOX, while 8 LOX, 12 LOX and 15 LOX catalyse the production of different lipoxins from 8 HPETE, 12 HPETE and 15 HPETE. Research on eicosanoids has mainly been mammalian driven and has lately been aimed at designing NSAIDs that are COX 2 selective due to the potential negative side effects of COX 1 inhibition, which may affect the gas trointestinal tract, heart and kidneys.

Eicosanoids act at both the extracellular and intracellular level by interact ing with distinct transmembrane G protein coupled receptors and nuclear peroxiso mal proliferator activated receptors. Activated Inhibitors,Modulators,Libraries G proteins may, depending on cell type, stimulate second messengers Inhibitors,Modulators,Libraries such as cyclic adenosine monophosphate andor intracellular calcium release. PPAR are transcription factors which also have a role in ligand bind ing, so directly influencing the expression Inhibitors,Modulators,Libraries of target genes involved in e. g. controlling prenatal and postnatal development. These examples emphasise the biological significance of eicosanoids. Less is known about eicosanoids in non mammalian spe cies.

however, during the last three decades considerable evidence has been gathered concerning their synthesis and action. Eicosanoids have now been identified in almost every major metazoan phyla including some plants. There is general consensus that eicosanoids act as autocrine or paracrine signallers in both vertebrates and invertebrates, where Inhibitors,Modulators,Libraries they mainly function as important mediators in reproduction, the immune system and ion transport. It is clear from a number of reports that eicosanoid gener ation is subject to inhibition by NSAIDs in a wide range of invertebrates. Moreover, a COX derived mechanism similar to the mammalian biosynthesis of PGs has been Inhibitors,Modulators,Libraries proposed in the coral Plexaura homomalla. There is also evidence of a LOX derived pathway being present in inver tebrates based on the work of Ragab and colleagues on the primitive wingless insect, the firebrat Thermobia domes tica.

although little is known about the structure of the pathway. enough Overall, invertebrate eicosanoid biosynthesis seems to have a simpler structure than its mammalian counterpart, as seen with the COX pathway, but also appears to be split into two instead of three pathways. There is currently no proof of an epoxygenase pathway being present in invertebrates.