Arachidonic Acid Signalling in the Nervous System

Nicolas G Bazan, Louisiana State University Health Sciences Center Neuroscience Center and Department of Ophthalmology, New Orleans, Louisiana, USA

Published online: January 2006

DOI: 10.1038/npg.els.0004045

Arachidonic acid integrates phospholipid molecules of cell membranes. When arachidonic acid is released it becomes itself a messenger or is the precursor of a wide variety of arachidonic acid-derived messengers. These bioactive lipids modulate the function of ion channels, receptors, neurotransmitter release, synaptic plasticity, glia–neuron relationships and programmes of neuronal gene expression. Therefore, arachidonic acid signalling participates in cell function and in certain pathologic conditions of the nervous system. The availability of arachidonic acid is regulated by the biosynthesis of specific phospholipids molecular species, their arachidonate remodelling, and the regulation of the release of arachidonic acid from membrane reservoirs and the subsequent conversion steps (e.g. cyclo-oxygenation, lipooxygenation).

Keywords: prostaglandins; leucotrienes; eicosanoids; cerebral ischaemia; seizures; thromboxane; free fatty acids

Figure 1. Arachidonic acid cyclo-oxygenation and peroxidation leads to the synthesis of a short-lived metabolite, PGH2. In turn, PGH2 is the substrate for several enzymes that lead to the synthesis of prostaglandins, thromboxanes and prostacyclin. G-protein-linked receptors are shown, along with some of their functions.
Figure 2. Arachidonic acid lipooxygenation. Lipooxygenase enzymes oxygenate arachidonic acid in different positions, thus they are named the 5-, 8-, 11-, 12-, and 15-lipooxygenases and catalyse reactions that produce messengers. This figure illustrates as an example the synthesis of leucotriene B4 and of sulfidopeptide leucotrienes (LTC4, D4 and E4), the 5-lipooxygenase pathway. It also depicts the synthesis of lipooxins by 15-lipooxygenase.
Figure 3. Calcium-dependent phospholipase A2 (cPLA2) and the generation of bioactive lipids during ischaemia and reperfusion. During the ischaemic phase, phospholipase overactivation and the downregulation of oxidative and energy metabolism, and hence reincorporation of cPLA2 metabolites, promote the accumulation of AA and lysophospholipids such as lyso-PAF. Reperfusion promotes the accumulation of pathophysiologically high levels of these mediators. Reactive oxygen radicals are generated at rates that may overload the antioxidant and free radical scavenger systems of the brain, thus allowing free radical damage to a range of molecules, including peroxidation of polyunsaturated fatty acids. FFA, free fatty acid; HETE, hydroxyeicosatrienoic acid; MAPK, mitogen-activated protein kinase. Further information on PAF can be found in Bazan (2003).
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Related Sub-Topics:

Ion Channels | Receptors for Neurotransmitters | Glia | Cell Membranes | Intracellular and Extracellular Signalling
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Article Title: Arachidonic Acid Signalling in the Nervous System
 
How to Cite close
Bazan, Nicolas G(Jan 2006) Arachidonic Acid Signalling in the Nervous System. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004045]