PLACENTAL BIOGENIC-AMINE TRANSPORTERS - CLONING AND EXPRESSION

During intrauterine development, catecholamine turnover (production an d clearance rates) is higher than under any other circumstances. This is mediated in large part by placental clearance of circulating catech olamines via a cocaine-sensitive, neuronal transporter-dependent mecha nism. In order to confirm the molecular mechanisms for placental trans port, we screened an ovine placental cDNA library for biogenic amine t ransporters. We report here the identification of two biogenic amine t ransporters with sequences very similar to their neuronal counterparts . One is an ovine serotonin transporter (oSERT) with > 90% homology to the human neuronal SERT. Expression studies confirm transport and com petitive binding affinities consistent with a SERT transporter. We hav e also isolated a partial sequence for the ovine norepinephrine transp orter (oNET). These results confirm the placental expression of plasma membrane biogenic amine transporters. We suggest the exaggerated feta l vulnerability to uptake inhibitors, Like cocaine, may be due to bloc kade of placental biogenic amine transport. (C) 1997 Elsevier Science B.V. All rights reserved.