Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites
ABSTRACT: 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 hOAT...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2003-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319325563 |
| _version_ | 1831664867511107584 |
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| author | Mahmoud Alebouyeh Michio Takeda Maristela Lika Onozato Akihiro Tojo Rie Noshiro Habib Hasannejad Jun Inatomi Shinichi Narikawa Xiu-Lin Huang Suparat Khamdang Naohiko Anzai Hitoshi Endou |
| author_facet | Mahmoud Alebouyeh Michio Takeda Maristela Lika Onozato Akihiro Tojo Rie Noshiro Habib Hasannejad Jun Inatomi Shinichi Narikawa Xiu-Lin Huang Suparat Khamdang Naohiko Anzai Hitoshi Endou |
| author_sort | Mahmoud Alebouyeh |
| collection | DOAJ |
| description | ABSTRACT: 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 IC50 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. |
| first_indexed | 2024-12-19T19:23:50Z |
| format | Article |
| id | doaj.art-4537976dc60644c2bd972f558d0400ea |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-19T19:23:50Z |
| publishDate | 2003-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-4537976dc60644c2bd972f558d0400ea2022-12-21T20:08:52ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01934430436Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter MetabolitesMahmoud Alebouyeh0Michio Takeda1Maristela Lika Onozato2Akihiro Tojo3Rie Noshiro4Habib Hasannejad5Jun Inatomi6Shinichi Narikawa7Xiu-Lin Huang8Suparat Khamdang9Naohiko Anzai10Hitoshi Endou11Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan; Neuroscience Research Center, Shahid Beheshti University Medical Sciences, Tehran, IranDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Nephrology and Endocrinology, University of Tokyo, Tokyo 113-8655, JapanDepartment of Nephrology and Endocrinology, University of Tokyo, Tokyo 113-8655, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanKobuchizawa Laboratories, Fuji Biomedixs Co., Yamanashi 408-0044, JapanKobuchizawa Laboratories, Fuji Biomedixs Co., Yamanashi 408-0044, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanABSTRACT: 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 IC50 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.http://www.sciencedirect.com/science/article/pii/S1347861319325563 |
| spellingShingle | Mahmoud Alebouyeh Michio Takeda Maristela Lika Onozato Akihiro Tojo Rie Noshiro Habib Hasannejad Jun Inatomi Shinichi Narikawa Xiu-Lin Huang Suparat Khamdang Naohiko Anzai Hitoshi Endou Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites Journal of Pharmacological Sciences |
| title | Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites |
| title_full | Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites |
| title_fullStr | Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites |
| title_full_unstemmed | Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites |
| title_short | Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites |
| title_sort | expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319325563 |
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