Platelet-activating factor (PAF) is the trivial name for 1-O-alkyl-2-acetyl-snglycero- 3-phosphocholine (Fig. 7.1). PAF is synthesized from a specific subclass of PtdCho, which contains an ether bond, rather than an ester bond at the sn-1 position of the glycerol backbone (Snyder, 1995; Bazan, 2003). PAF production is tightly regulated both at the synthetic and degradative levels. PAF is released by a wide variety of cells, including neural cells, macrophages, platelets, endothelial cells, mast cells, and neutrophils. It causes neutrophil adhesion, chemotaxis, increased vascular permeability, and vasodialation. Although the synthesizing enzymes have not been purified and fully characterized from brain tissue, reports on the synthesis of PAF in mammalian brain are beginning to emerge (Francescangeli et al., 2000). PAF is synthesized in neural cells either spontaneously or under appropriate stimulation. In neuronal and glial cell cultures, acetylcholine dramatically stimulates PAF synthesis, and addition of cholinergic receptor antagonist, atropine, produces the inhibition of PAF synthesis (Sogos et al., 1990). PAF induces a significant mobilization of intracellular free Ca2+, which is inhibited by PAF antagonists. The increase in Ca2+ is not only caused by the release from intracellular stores, but also through calcium influx via calcium channels. In neurons, PAF receptors are linked through guanine nucleotide-binding proteins (G proteins) to phospholipase C (PLC), and receptor-operated Ca2+ channels that are modulated by protein kinase C (PKC). Both PTX-sensitive and insensitive G proteins appear to be coupled with the PAF receptor, producing the activation of PLC and the increase in intracellular Ca2+. Thus, in neurons, PAF action is associated with PLC and PKC-mediated signal transduction processes (Yue et al., 1992; Farooqui et al., 2008). In astrocytes, PAF upregulates nerve growth factor mRNA in a time and concentration-dependent manner. This increase in nerve growth factor mRNA is suppressed by WEB 2086 and BN52021, potent PAF antagonists (Brodie, 1995; Yoshida et al., 2005). PAF may be involved in interactions between astroglial cells and neurons. Astrocytic PAF may provide a neurotrophic signal to injured neurons. It is suggested that interplay between PAF and the neurotrophic receptor may be involved in regenerative processes in the brain tissue. In brain, the physiological activity of PAF is not limited to its proinflammatory function, neurotoxicity, apoptosis, and blood–brain barrier permeability, but also associated with neurotrophic effects. In nonneural tissues, PAF is also involved in a variety of other settings including reproduction, allergic reactions, and circulatory system disturbances such as atherosclerosis (Chao and Olson, 1993; Honda et al., 2002; Bazan, 2003).
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(2008). Synthesis of Platelet-Activating Factor in Brain. In: Metabolism and Functions of Bioactive Ether Lipids in the Brain. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77401-5_7
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