How Do Eicosanoids Exit Cells

Arachidonate is mobilized in the cell s interior, and all eicosanoid-synthesizing enzymes are intracellular. Yet, aside from second messenger roles, such as those illustrated in the previous sections, all other actions of the eicosanoids take place in the extracellular milieu, where these molecules can interact with transmembrane receptors. How do the eicosanoids exit the cells in which they are produced  

It is often assumed that lipid molecules can readily traverse cell membranes by passive diffusion and freely access all cellular compartments without the need for any transport system. Despite its persistent popularity, this simplistic view is not likely to be correct. Strongly ionized lipids, such as phosphatidylcholine, are expected, of course, to require transport proteins because their charge would limit membrane diffusion. Indeed, ATP-dependent translocases that selectively extrude phospholipids from cells have 

A number of studies over the past 10 years have described the kinetic properties and protease sensitivities of cellular fatty acid transfer systems. A general conclusion of these studies is that fatty acid transfer cannot be accounted for simply by a process of passive diffusion. Moreover, at least three structurally different plasma membrane proteins that may mediate fatty acid transport have been identified by molecular cloning and expression in heterologous systems. These are the fatty acid transporter (FAT), the fatty acid transport protein (FATP) and the plasma membrane fatty acid-binding protein (FABPp ,).  

The discovery of PGT is quite recent, and many questions still lie ahead. We don t know yet if PGT is the only protein dedicated to prostanoid transport in mammalian tissues. Neither do we know of selective drugs that can block its activity. These issues are relevant, not only to our understanding of prostanoid biology, but also, in light of the multiple roles of the prostaglandins in disease, to the development of novel classes of therapeutic agents. 

The existence of export carriers for the leukotrienes has also been postulated, mainly on the grounds of the hydrophilic properties of these compounds. LTC4, for example, contains a glutathione moiety that would presumably hinder the molecule s diffusion through cell membranes. 

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