Analysis of Endogenous Metabolite Transporters for the Development of Novel Pharmaceutical Therapies and Drug Targets

Author:
Publisher website
Google Scholar
Abstract
Transporters are critical for maintaining the homeostasis of metabolites within cells, organelles, and extracellular fluids. Various transporters have been targeted for development as pharmaceutical therapies, including glucose transporter (SLC5A2/ SGLT2) and urate transporter (SLC22A12/URAT1). The solute carrier transporter family includes many orphan transporters with unknown physiological functions and substrates, largely because of the difficulties in optimizing the transporter probes and constructing convenient evaluation systems for functional analysis. However, the analysis of these transporters is important as they may be potential candidates for pharmaceutical therapies or drug targets. This review focuses on the analysis of the SLC16A family, which encodes monocarboxylate transporters (MCTs), as it contains orphan transporters known to be associated with several disease pathologies. We successfully identified taurine, cephradine, and 5-carboxyfluorescein as new substrates for rat Slc16a6/MCT7, SLC16A13/MCT13, and SLC16A5/MCT6, respectively. These substrates enabled the functional analysis of the transporters in mammalian cells. We found that the co-expression of ancillary proteins, such as ancillary protein basigin/CD147 and embigin/GP70, enhanced the transport functions of these transporters. Interestingly, the functions of MCT6 and MCT13 were affected by extracellular chloride and potassium ions, respectively, but MCT7 was unaffected. These findings are helpful for elucidating the pathophysiological roles and substrates of orphan and uncharacterized MCTs.

This publication has 13 references indexed in Scilit: