Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes
and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small
molecule transporter families have been found in the podocyte membrane, but expression and function of membrane
transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules
which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA). We
observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA,
suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes
express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion
Transporter Polypeptides (OATP/Oatp) family of influx transporters, and P-glycoprotein, a member of the MultiDrug
Resistance (MDR) efflux transporter family. Expression of OATP/Oatp transporters was modified by PA treatment. Similarly,
in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the
engagement of the molecule upon PA administration. In summary, we have characterized some of the small molecule
transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further
investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte
homeostasis and in the pathogenesis of podocyte injury.
