An update on the extraneuronal monoamine transporter (EMT): characteristics, distribution and regulation.

Biological membranes prevent transmembrane diffusion in the majority of organic molecules that bear net charges at physiological pH. Consequently, these compounds must use more or less specific membrane-bound transport systems to be imported into or exported from cells or organisms. The extraneuronal monoamine transporter (EMT) is a transmembranar transport system involved in the transfer of monoamine compounds across cell membranes. It was identified more than 30 years ago [1], its functional characteristics being thereafter described [review by 2]. The recent cloning of this transporter in man and rat reopened investigation and interest in this entity. EMT is a Na(+) and Cl(-)-independent, potential-dependent carrier, known to have a broad tissue distribution (eg. myocardium, vascular and non-vascular smooth muscle cells, glandular cells, placenta and CNS glial cells). According to its transport function and primary structure, EMT is included in the amphiphilic solute facilitator (ASF) family of transporters. Physiological substrates for EMT include the monoamines serotonin, dopamine, noradrenaline, adrenaline and histamine. Moreover, several xenobiotics including the neurotoxin 1-methyl-4-phenylpyridinium, clonidine, cimetidine and the K(+)-channel blocker tetraethylammonium interact with this transporter. The aim of this work is to review knowledge concerning EMT, making an update on its functional characteristics, physiological importance and regulation. A special emphasis will be given to very recent investigations concerning regulation of EMT by intracellular second messenger systems and the interaction of modulators of P-glycoprotein, the product of the multidrug resistance gene MDR1, with EMT.