Histamine elimination from the cerebrospinal fluid across the blood–cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4)

• Published in: Journal of neurochemistry Vol. 139; no. 3; pp. 408 - 418
• Main Authors: Usui, Takuya, Nakazawa, Ayumi, Okura, Takashi, Deguchi, Yoshiharu, Akanuma, Shin‐ichi, Kubo, Yoshiyuki, Hosoya, Ken‐ichi
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2016
• Subjects: Animals; Blood-Brain Barrier - metabolism; Blood-Nerve Barrier - metabolism; blood–cerebrospinal fluid barrier; Body fluids; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Cell Membrane - metabolism; CHO Cells; choroid plexus; Choroid Plexus - metabolism; Cricetinae; Cricetulus; Equilibrative Nucleoside Transport Proteins; Histamine; Histamine - administration & dosage; Histamine - cerebrospinal fluid; Histamine - pharmacology; In Vitro Techniques; Injections, Intraventricular; Lopinavir - pharmacology; Male; Microinjections; narcolepsy; Neurochemistry; Plasma; plasma membrane monoamine transporter; Protease Inhibitors - pharmacology; Rats; Rats, Wistar; blood-cerebrospinal fluid barrier; histamine; plasma membrane monoamine transporter; narcolepsy; choroid plexus
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.13758

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. The elimination of histamine, an excitatory neurotransmitter, from the brain/CSF across the blood–brain barrier and blood–CSF barrier (BCSFB) was investigated. This study demonstrated that the BCSFB plays an important role in the elimination of histamine from the CSF, and plasma membrane monoamine transporter (PMAT/SLC29A4) is responsible for this process. Our findings provide a novel insight into the role of PMAT at the BCSFB in the homeostasis of the cerebral histamine concentration.