Foreword

Membrane transporters, which are integral transmembrane proteins, play various biological and physiological roles by controlling the trafficking of specific compounds across biological membranes and, thereby, being involved in their disposition locally in cells and organs, and systemically throughout the body. They can be categorized into several types, based on their functions and roles. A major type of transporters includes those that operate for the cellular uptake of solutes, most typically nutrients that are needed to maintain cells and the living body to survive. Another major type of transporters includes those that operate for the cellular secretion of solutes, most typically metabolic wastes and xenobiotics that have to be extruded out of cells and ultimately out of the living body for its survival. There are also many other types of transporters that operate for cellular solute uptake or secretion with miscellaneous roles and those that operate at organelle membranes for solute trafficking associated with physiological activities within the cell.

With the advancement of molecular identification of transporters in recent years, these molecules have been increasingly recognized to be involved in the transport of a variety of drugs and, thereby, in drug disposition in the body. Understanding the functions and roles of transporters involved in drug disposition has accordingly been recognized to be of great help in developing drugs with favorable disposition characteristics and in devising optimized therapeutic uses of drugs, for example, to avoid adverse events that could arise from drug interactions at transporters. Thus research on transporters has grown and developed extensively with an emphasis on their involvement in drug disposition in the field of pharmaceutical sciences and relevant disciplines. Another aspect that has been of interest is to exploit transporters as targets for the development of drugs and therapeutic strategies, including transporter-mediated local delivery of drugs into cells and organs as the target sites of drug action. Although this aspect of research seems to be rather slow in development, several classes of drugs that act on transporters are in therapeutic use. Among them are the inhibitors of sodium-dependent glucose transporter 2 (SGLT2) for the treatment of diabetes, which have been most recently developed. Transporter-mediated local delivery of drugs, which could be closely linked to drug action, is also of interest as a part of the overall process of drug action at the target site. In this context, transporters could be exploited to elicit drug action effectively as the pathways of drug supply in therapeutic strategies. Expectations are now high for accelerated development of research for such exploitation of transporters in various aspects. The present Current Topics is intended to provide reviews of seminal studies oriented to those directions.

The first article by Inoue reviews studies on purine nucleobase transporters, including equilibrative nucleobase transporter 1 (ENBT1/SLC43A3), which has mostly recently been identified and suggested to be exploited as a ganciclovir (GCV) transporter that may be effective in cancer therapy. The second article by Kubo et al. reviews studies on several types of cation transporters that have been functionally identified at the blood–retinal barrier. These transporters may be exploited for retinal delivery of cationic neuroprotectants for the treatment of retinal diseases. The third article by Nakamichi and Kato reviews studies on carnitine/organic cation transporter 1 (OCTN1), focusing on its role as a transporter for the uptake of ergothioneine (ERGO) in neural cells in the brain. ERGO, which is a food-derived antioxidant, has been suggested to be involved in suppressing various neurological disorders and, hence, OCTN1 may be exploited as a target of its enhancing drugs for the treatment of such disorders. The last article by Furihata and Anzai reviews studies on organic ion transporters in astrocytes in the brain, focusing on organic cation transporter 3 (OCT3), plasma membrane monoamine transporter (PMAT), carnitine/organic cation transporter 2 (OCTN2), and organic anion transporting polypeptide 1C1 (OATP1C1). These transporters have been suggested to be involved in neurotransmission and some other brain functions through the uptake of their specific substrates into astrocytes and, hence, they may be exploited as targets of their modulating drugs for the treatment of brain disorders.

These reviews would be of help in facilitating and guiding future development of research for exploitation of transporters as targets for the development of drugs and therapeutic strategies.