Estudio electrofisiológico de la selectividad del transportador de nucleósidos hCNT2 y de las propiedades electrogénicas de los transportadores de ácidos biliares OATP1B1 y OATP1B3

Resumen

UNIVERSITY OF NAVARRA FACULTY OF SCIENCES ELECTROPHYSIOLOGICAL STUDY OF THE NUCLEOSIDE TRANSPORTER hCNT2 SELECTIVITY AND OF THE ELECTROGENIC PROPERTIES OF THE BILE ACID TRANSPORTERS OATP1B1 AND OATP1B3 CARLOS SANCHO MATEO 2012 The human concentrative nucleoside transporter 2 (hCNT2), is a Na+ dependent concentrative nucleoside cotransporter selective for purine nucleosides and urdine that can also transport nucleoside derivatives used in antiviral and anticancer therapies. In the present work, we have expressed hCNT2 in Xenopus laevis oocytes, and used the two-electrodes voltage-clamp technique to study its interaction with a series of uridine and adenosine derivatives used in therapeutic treatments and synthesized in our university. The comparison of the kinetic parameters of the derivatives transported by hCNT2 with those corresponding to the transport by hCNT3 and hCNT1 demonstrates that hCNT2 is the most restrictive transporter among the human isoforms. It is also most restrictive that rat CNT2. The differences on the structural requirements of rat CNT2 and human CNT2 have implication on the experimental model used for the studies about the interaction of the transporters with drugs. Using the same technique, we have also studied the electrogenic properties of the human organic anion transporter polypeptides type 1 and type 3, OATP1B1 and OATP1B3. We demonstrate for the first time that these transporters are electrogenic showing two types of currents: a current associated to the transport of the substrates and a Na+ current uncoupled to the substrate transport (Na+ leak current). These properties will allow the study of the functional mechanism of these transporters using electrophysiological methods.