Eicosanoid functions

See also Prostaglandin Biosynthesis, NSAIDs, Eicosanoid Functions... 

Funk, C.D. (1996) The molecular biology of mammalian lipoxygenases and the quest for eicosanoid functions using lipoxygenase-deficient mice, Biochim. Biophys. Acta 1304,65-84... 

Mead JF (1984) The non-eicosanoid functions of the essential fatty adds. J Lipid Res 25 1517-1521... 

CP 55940 (79) and nabilone (80) are synthetic ligands for the cannabiaoid receptor. However, the identification of the eicosanoid, anandamide (81), as an endogenous cannabimimetic has provided an important tool to study cannabiaoid receptor function. 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

Some fatty acids are not synthesized by mammals and yet are necessary for normal growth and life. These essential fatty aeids include llnoleic and y-linolenic acids. These must be obtained by mammals in their diet (specifically from plant sources). Arachidonic acid, which is not found in plants, can only be synthesized by mammals from linoleic acid. At least one function of the essential fatty acids is to serve as a precursor for the synthesis of eicosanoids, such as... 

CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vaso-dilatory, and fibrinolytic properties. Polymorphic alleles with reduced function are known. Some other CYP2 subfamilies and isozymes listed in Table 1 are still not well characterized, in part because most of them were discovered in the course of the human genome project. 

Besides watet, the diet must provide metaboEc fuels (carbohydrate and fat) fot bodily growth and activity protein fot synthesis of tissue proteins fiber for roughage minerals for specific metabolic functions cettain polyunsamtated fatty acids of the n-3 and n-6 famihes fot eicosanoid synthesis and other functions and vitamins, otganic compounds needed in small amounts for many varied essential functions. 

It is misleading to consider that ROS are always deleterious, and that to prevent release or action of ail ROS will be of therapeutic value. One could reason that some ROS are released without control or purpose, as by-products of the normal metabolism of eicosanoids, or during oxidative phosphorylation in the mitochondria. However, during normal function, inflammatory ceUs appropriately release ROS both intracellularly into vacuoles and extracellularly in order to kill foreign organisms in host defence. Also, nitric oxide is a radical species whose principal role in the lung appears to be the control of pulmonary vascular tone and platelet function. Nevertheless, there are clear examples where fhistrated phagocytosis could explain an excessive release of ROS in... 

FIGURE 57-2. Eicosanoid synthesis pathway. Cyclooxygenase is inhibited by nonsteroidal anti-inflammatory drugs and aspirin. (From Widmaier EP, Raff H, Strang KT, et al, (eds.) Vander, Sherman, Luciano s Human Physiology The Mechanisms of Body Function. 9th ed. New York McGraw-Hill 2004, Figure 5-11.)... 

Bandeira-Melo C, Bozza PT, Weller PF. The cellular biology of eosinophil eicosanoid formation and function. J Allergy Clin Immunol 2002 109(3) 393-400. 

TNF activates inflammatory functions of various immune cells, not only as a direct effector but also as part of the cytokine network (synergism with IL-1, IFN-y, and LPS), as shown in Table 2 (K11). TNF interacts with the complement system and induces the additional release of eicosanoids. TNF has many effects on... 

It is a pro-inflammatory cytokine, promoting the synthesis of various substances such as eicosanoids, as well as proteases and other enzymes involved in generating inflammatory mediators. This appears to be its major biological function. 

Reports that AA is released primarily by G-protein-mediated PLA2 activation remain to be confirmed [84, 85]. In addition, modulation of PLA2 by Ca2+ and protein kinase needs to be better defined. It is clear that NMDA receptor activation promotes the release of AA [86], and that a variety of eicosanoids are then generated (Fig 33-2,33-3). The modulatory events that channel AA towards specific eicosanoids are not understood. The endocannabinoid family of lipid messengers will remain an active focus of interest because of the growing evidence of their actions in synaptic function, learning, memory, and other forms of behavior [56,87]. 

Dietary polyunsaturated fatty acids (PUFAs), especially the n-3 series that are found in marine fish oils, modulate a variety of normal and disease processes, and consequently affect human health. PUFAs are classified based on the position of double bonds in their lipid structure and include the n-3 and n-6 series. Dietary n-3 PUFAs include a-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) whereas the most common n-6 PUFAs are linoleic acid, y-linolenic acid, and arachidonic acid (AA). AA is the primary precursor of eicosanoids, which includes the prostaglandins, leukotrienes, and thromboxanes. Collectively, these AA-derived mediators can exert profound effects on immune and inflammatory processes. Mammals can neither synthesize n-3 and n-6 PUFAs nor convert one variety to the other as they do not possess the appropriate enzymes. PUFAs are required for membrane formation and function... 

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