Transport of dopamine and levodopa and their interaction in COS-7 cells heterologously expressing monoamine neurotransmitter transporters and in monoaminergic cell lines PC12 and SK-N-SH.
The present study investigated the effects of levodopa, a precursor of dopamine (DA) therapeutically used for the treatment of Parkinson's disease, on DA transport in the two different systems, COS-7 cells heterologously expressing rat monoamine transporter cDNA and in monoaminergic cell lines PC12 and SK-N-SH. Levodopa enhanced uptake of [3H]DA and [3H]norepinephrine (NE) but not [3H]serotonin in the transfected COS-7 cells in a concentration-dependent manner. On the other hand, in PC12 and SK-N-SH cells where NET is functionally expressed, levodopa enhanced [3H]DA and [3H]NE uptake at low concentrations and inhibited the uptake at higher concentrations. The effects of levodopa on catecholamine transporters in the opposite direction suggest a different mechanism at the intra- and extracellular sites in a levodopa transport-dependent and independent manner.
Hashimoto
W
W
Department of Dental Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan.
Kitayama
S
S
Kumagai
K
K
Morioka
N
N
Morita
K
K
Dohi
T
T
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002522:Chlorocebus aethiops; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007980:Levodopa / Q000378:metabolism* / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D014162:Transfection
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015306:Biogenic Monoamines; D002352:Carrier Proteins; D002395:Catecholamines; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D007980:Levodopa; D001142:Aromatic-L-Amino-Acid Decarboxylases; D003042:Cocaine; D004298:Dopamine