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

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 [³ H]histamine from the rat brain across the blood-brain barrier. The [³ H]histamine elimination clearance from the rat CSF was 3.8-fold greater than that of a CSF bulk flow marker, and the elimination of [³ H]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 [³ H]histamine by the isolated rat choroid plexus revealed histamine elimination from the CSF across the BCSFB. The [³ H]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, [³ H]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.

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