Received for publication October 26, 2007.
Revised January 10, 2008.
Accepted for publication January 10, 2008.

The role of the multidrug transporter proteins ABCB1 and ABCC2 in the diaplacental transport of talinolol in the term human placenta

Abstract

Placental syncytiotrophoblasts are known to express the efflux transporter proteins P-glycoprotein (ABCB1, P-gp) and multidrug resistance-associated protein 2 (ABCC2, MRP2), which are supposed to be a functional part of the human placental barrier. With advancing gestational age, expression of ABCB1 decreases progressively whereas ABCC2 is more expressed. To evaluate to which extent they contribute to placental barrier function at term, permeability of talinolol, a substrate of both carriers, was measured using a validated human placenta perfusion model. We identified in randomized, cross-over experiments an unidirectional transfer of talinolol in feto-maternal direction because the materno-fetal transfer was significantly lower (0.663 ± 0.188 versus 0.394 ± 0.067 relative to creatinine permeability, p=0.012). Materno-fetal permeability was increased by the ABCC2 inhibitor probenecid (0.59 ± 0.15 versus 0.68 ± 0.13, p=0.028) and the non-specific inhibitor verapamil (0.53 ± 0.09 versus 0.66 ± 0.16, p=0.028) but was not influenced by the ABCB1 inhibitor PSC833 (0.48 ± 0.11 versus 0.46 ± 0.09, p=0.345). Genetic polymorphisms of ABCB1 and ABCC2 lacked significant influence on expression of the carriers and permeability of talinolol, respectively. Conclusion: Materno-fetal transfer of talinolol is restricted by a unidirectional process that is influenced by inhibitors of ABCC2.

Key words: ABC transporters, drug transport, MRP, p-glycoprotein