Aquatic invertebrates open up new perspectives in eicosanoid research: Biosynthesis and bioactivity

Abstract

Since the chemical characterisation of prostaglandins (PGs) in the early 1960s (I), research on these and other products of the oxidative metabolism of polyunsaturated fatty acids (PUFAs), termed ‘oxylipins’ by Gerwick et al (2), has been proceeding to an ever increasing pace. The variety of arachidonic acid (AA) derivatives, also known as eicosanoids, their possible pharmacological actions in all aspects of mammalian physiology and the biochemical pathways leading to their synthesis, seems to be limitless. Apart from cycloxygenase-derived PGs. AA can be enzymatically oxidised to hydroxyeicosatetraenoic acids (HETEs), leukotrienes (LTs) and lipoxins (LXs) through the action of enantioselective S-lipoxygenases (3,4). Cytochrome P450 monoxygenases catalyse the formation of HETEs, hepoxy-, diand trihydroxyeicosatetraenoic acids (hepoxilins, di-HETEs and trioxilins; 5). Apart from extensive research in mammals, recent efforts have been made to establish the occurrence and physiological relevance of eicosanoids and other oxylipins in invertebrates. With so much work yet to be performed in mammals, the necessity of undertaking analogous investigations in lower forms of life could be questioned. Nevertheless. the importance in nature of enzq matic PUFA oxidation is being currently underlined by these studies, where a high degree of conservation for many of the metabolic pathways mentioned above, throughout most phyla of the animal kingdom and, therefore. during the course of evolution, is found (6). The need for studies on invertebrate eicosanoids goes beyond simple comparative and evolutionistic considerations. Animals less complex and organised than mammals have been widely used as simple systems where various aspects of cell biology can be investigated where a smaller number of parameters have to be considered. The aim of the present review is to demonstrate how eicosanoid research can benefit from investigations in non-mammalian organisms, in particular in aquatic invertebrates. These investigations, apart from extending findings previously reported in mammals, have led to the discovery of: (A) new eicosanoid metabolic pathways. enzymatic activities and chemical structures; (B) unprecedented biological functions, in some cases described later also in higher vertebrates. and (C) a role for eicosanoids in invertebrate adaptation to various environmental situations. A bipolar attitude has so far characterised research on invertebrate oxygenated PUFAs. On one hand, chemical studies have established that lower organisms generate many PUFA metabolites of unprecedented structure but whose biosynthesis and biological function has subsequently not been fully investigated. Conversely, many investigations on the effect of mammalian eicosanoids on functions of several aquatic lower animals have been scrupulously investigated without establishing the chemical structure of the metabolites involved or whether they are actually present in the organisms under study. Both these typological investigations have been comprehensively described by several previous reviews (7-l 1). Therefore, the present article will focus mainly on those studies which have provided insights in both biochemical and physiological aspects of aquatic invertebrate organisms and shown new drections for future research in this fascinating, ever expanding and seemingly inexhaustible field.