Placental biogenic amine transporters: cloning and expression.
During intrauterine development, catecholamine turnover (production and clearance rates) is higher than under any other circumstances. This is mediated in large part by placental clearance of circulating catecholamines via a cocaine-sensitive, neuronal transporter-dependent mechanism. In order to confirm the molecular mechanisms for placental transport, we screened an ovine placental cDNA library for biogenic amine transporters. We report here the identification of two biogenic amine transporters 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 competitive binding affinities consistent with a SERT transporter. We have also isolated a partial sequence for the ovine norepinephrine transporter (oNET). These results confirm the placental expression of plasma membrane biogenic amine transporters. We suggest the exaggerated fetal vulnerability to uptake inhibitors, like cocaine, may be due to blockade of placental biogenic amine transport.
Padbury
J F
JF
Department of Pediatrics, Women and Infants Hospital of Rhode Island, Brown University School of Medicine, Providence 02905-2499, USA. james_padbury@brown.edu
Tseng
Y T
YT
McGonnigal
B
B
Penado
K
K
Stephan
M
M
Rudnick
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D012756:Sheep
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin