Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

Abstract

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 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.

Interactions of Organic Anion Transporters and Organic Cation Transporters With Mycotoxins

“…In this regard, we found that hOAT3 mRNA is expressed in the brain (34), and the localization of hOAT1 in the blood-brain barrier was recently confirmed immunohistochemically (35). In the current study, we revealed that hOAT1 and hOAT3 mediates the transport of aflatoxin B1.…”

Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias

“…In the present study, we report on the capability of OATs to transport GA derivatives across membranes. Since these transporters are present also in the brain [18], OATs may not only influence plasma levels of GA derivatives by securing their renal excretion but may also have an important impact on their levels in brain tissue.…”

Identification of a New Urate and High Affinity Nicotinate Transporter, hOAT10 (SLC22A13)

“…Most of these are highly expressed in the kidneys (OAT1-OAT4, Oat5, Oat v 1, and URAT1), whereas Oat6 is only expressed in the olfactory bulb, and the recently identified human OAT7 is currently the only liver-specific OAT. The substrate panel of OATs includes important endogenous compounds like urate (15)(16)(17), prostaglandins (18), neurotransmitter and tryptophan metabolites (19,20), sulfated steroids, and a long list of drugs such as anti-viral drugs, antibiotics, antidotes (21), or diuretics (22)(23)(24).…”