Involvement of l-type amino acid transporter 1 in the transport of gabapentin into human placental choriocarcinoma cells.
Gabapentin (GBP) is a widely used antiepileptic drug, with potential for use in the treatment of epilepsy in pregnant women. Although studies have examined GBP transport mechanisms across the blood-brain barrier, kidney, and intestine, the mechanism in the placenta has not been fully elucidated. We previously reported that GBP accumulates at high concentrations in human placental choriocarcinoma BeWo cells. The purpose of this study was to examine the transport mechanism of GBP in placental choriocarcinoma cells (BeWo and JEG-3), and to identify the carrier involved. High concentrations of intracellular GBP accumulations were also found in JEG-3 cells. A kinetic analysis showed that a single carrier system was involved in the uptake of GBP. Furthermore, substrates for l-type amino acid transporter (LAT) and siRNAs targeted to LAT1 significantly decreased GBP uptake. Our observations from this study suggest that LAT1 is the main contributor to GBP transport in placental choriocarcinoma cells.
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Ayako
A
Furugen
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Yuri
Y
Ishiguro
Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan.
Masaki
M
Kobayashi
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Katsuya
K
Narumi
Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan.
Ayako
A
Nishimura
Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan.
Takeshi
T
Hirano
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan; Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan. Electronic address: ken-i@pharm.hokudai.ac.jp.
Ken
K
Iseki
D000588:Amines / Q000378:metabolism / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D000077206:Gabapentin; D055785:Gene Knockdown Techniques; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000493:pharmacokinetics*
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D027283:Large Neutral Amino Acid-Transporter 1; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
BeWo cells; Gabapentin (GBP); JEG-3 cells; Organic cation/carnitine transporter (OCTN); Placenta; l-type amino acid transporter (LAT)