title: Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4).
abstract: The elimination of histamine, an excitatory neurotransmitter, from the brain/CSF across the blood-brain barrier and blood-CSF barrier (BCSFB) was investigated using Wistar rats, which were anesthetized with pentobarbital sodium. An in vivo intracerebral microinjection study suggested that there was only partial efflux of [3H]histamine from the rat brain across the blood-brain barrier. The [3H]histamine elimination clearance from the rat CSF was 3.8-fold greater than that of a CSF bulk flow marker, and the elimination of [3H]histamine was significantly inhibited by the co-administration of unlabeled histamine, suggesting the involvement of a carrier-mediated process in histamine elimination from the CSF. The uptake study of [3H]histamine by the isolated rat choroid plexus revealed histamine elimination from the CSF across the BCSFB. The [3H]histamine uptake by TR-CSFB3 cells, a model cell line for the BCSFB, exhibited temperature-dependent and saturable kinetics, suggesting the involvement of carrier-mediated transport of histamine at the BCSFB. In the inhibition study, [3H]histamine uptake by TR-CSFB3 cells was significantly inhibited by substrates and/or inhibitors of plasma membrane monoamine transporter (PMAT/SLC29A4), but not affected by substrates of organic cation transporters. These results suggest the elimination of histamine from the CSF via plasma membrane monoamine transporter at the BCSFB.
authors: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Takuya
authors: T
authors: Usui
authors: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Ayumi
authors: A
authors: Nakazawa
authors: Laboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, Itabashi, Tokyo, Japan.
authors: Takashi
authors: T
authors: Okura
authors: Laboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, Itabashi, Tokyo, Japan.
authors: Yoshiharu
authors: Y
authors: Deguchi
authors: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Shin-Ichi
authors: SI
authors: Akanuma
authors: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Yoshiyuki
authors: Y
authors: Kubo
authors: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. hosoyak@pha.u-toyama.ac.jp.
authors: Ken-Ichi
authors: KI
authors: Hosoya
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D049428:Blood-Nerve Barrier / Q000378:metabolism*; D016466:CHO Cells; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D033705:Equilibrative Nucleoside Transport Proteins; D006632:Histamine / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D061466:Lopinavir / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D027682:Cation Transport Proteins; D033705:Equilibrative Nucleoside Transport Proteins; D011480:Protease Inhibitors; C000620660:SLC29A4 protein, rat; D061466:Lopinavir; D006632:Histamine
keywords: blood-cerebrospinal fluid barrier; choroid plexus; histamine; narcolepsy; plasma membrane monoamine transporter