Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites.
The purpose of the present study was to elucidate the expression of human organic anion transporter 1 (hOAT1) and hOAT3 in the choroid plexus of the human brain and their interactions with neurotransmitter metabolites using stable cell lines. Immunohistochemical analysis revealed that hOAT1 and hOAT3 are expressed in the cytoplasmic membrane and cytoplasm of human choroid plexus. Neurotransmitter metabolites, namely, 5-methoxyindole-3-acetic acid (5-MI-3-AA), homovanillic acid (HVA), vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HI-3-AA), N-acetyl-5-hydroxytryptamine (NA-5-HTT), melatonin, 5-methoxytryptamine (5-MTT), 3,4-dihidroxymandelic acid (DHMA), 5-hydroxytryptophol, and 5-methoxytryptophol (5-MTP), but not methanephrine (MN), normethanephrine (NMN), and 3-methyltyramine (3-MT), at 2 mM, inhibited para-aminohippuric acid uptake mediated by hOAT1. On the other hand, melatonin, 5-MI-3-AA, NA-5-HTT, 5-MTT, 5-MTP, HVA, 5-HI-3-AA, VMA, DOPAC, 5-hydroxytryptophol, and MN, but not 3-MT, DHMA, and NMN, at 2 mM, inhibited estrone sulfate uptake mediated by hOAT3. Differences in the IC(50) values between hOAT1 and hOAT3 were observed for DHMA, DOPAC, HVA, 5-HI-3-AA, melatonin, 5-MI-3-AA, 5-MTP, 5-MTT, and VMA. HOAT1 and hOAT3 mediated the transport of VMA but not HVA and melatonin. These results suggest that hOAT1 and hOAT3 are involved in the efflux of various neurotransmitter metabolites from the cerebrospinal fluid to the blood across the choroid plexus.
Alebouyeh
Mahmoud
M
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Takeda
Michio
M
Onozato
Maristela Lika
ML
Tojo
Akihiro
A
Noshiro
Rie
R
Hasannejad
Habib
H
Inatomi
Jun
J
Narikawa
Shinichi
S
Huang
Xiu-Lin
XL
Khamdang
Suparat
S
Anzai
Naohiko
N
Endou
Hitoshi
H
D002460:Cell Line; D002831:Choroid Plexus / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014642:Vanilmandelic Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D014642:Vanilmandelic Acid; D008550:Melatonin; D006719:Homovanillic Acid