Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in peripheral blood cells: relevance for physiology and pharmacotherapy.

摘要

Adenosine triphosphate-binding cassette (ABC)-type transport proteins were initially described for their ability to reduce intracellular concentrations of anticancer compounds, thereby conferring drug resistance. In recent years, expression of this type of proteins has also been reported in numerous cell types under physiological conditions; here, these transporters are often reported to alter systemic and local drug disposition (e.g. in the brain or the gastrointestinal tract). In this context, peripheral blood cells have also been found to express several ABC-type transporters. While erythrocytes mainly express multidrug resistance protein (MRP) 1, MRP4 and MRP5, which are discussed with regard to their involvement in glutathione homeostasis (MRP1) and in the efflux of cyclic nucleotides (MRP4 and MRP5), leukocytes also express P-glycoprotein and breast cancer resistance protein. In the latter cell types, the main function of efflux transporters may be protection against toxins, as these cells demonstrate a very high turnover rate. In platelets, only two ABC transporters have been described so far. Besides MRP1, platelets express relatively high amounts of MRP4 not only in the plasma membrane but also in the membrane of dense granules, suggesting relevance for mediator storage.In addition to its physiological function, ABC transporter expression in these structures can be of pharmacological relevance since all systemic drugs reach their targets via circulation, thereby enabling interaction of the therapeutic agent with peripheral blood cells. Moreover, both intended effects and unwanted side effects occur in peripheral blood cells, and intracellular micropharmacokinetics can be affected by these transport proteins. The present review summarises the data available on expression of ABC transport proteins in peripheral blood cells.