Histamine Clearance Through Polyspecific Transporters in the Brain.
Histamine plays an important role as a neurotransmitter in diverse brain functions, and clearance of histamine is essential to avoid excessive histaminergic neuronal activity. Histamine N-methyltransferase, which is an enzyme in the central nervous system that metabolizes histamine, is localized to the cytosol. This suggests that a histamine transport process is essential to inactivate histamine. Previous reports have shown the importance of astrocytes for histamine transport, although neuronal histamine transport could not be ruled out. High-affinity and selective histamine transporters have not yet been discovered, although it has been reported that the following three polyspecific transporters transport histamine: organic cation transporter (OCT) 2, OCT3, and plasma membrane monoamine transporter (PMAT). The Kmvalues of human OCT2, OCT3, and PMAT are 0.54, 0.64, and 4.4 mM, respectively. The three transporters are expressed in the brain, and their regional distribution is different. Recent studies revealed the contribution of OCT3 and PMAT to histamine transport by primary human astrocytes. Several investigations using mice supported the importance of OCT3 for histamine clearance in the brain. However, further studies are required to elucidate the detailed mechanism of histamine transport in the brain.
Department of Pharmacology, Tohoku University, Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. tyoshikawa@med.tohoku.ac.jp.
Takeo
T
Yoshikawa
Department of Pharmacology, Tohoku University, Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Kazuhiko
K
Yanai
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D033705:Equilibrative Nucleoside Transport Proteins / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*
D033705:Equilibrative Nucleoside Transport Proteins; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D006632:Histamine
Diamine oxidase; Histamine; Histamine N-methyltransferase; Organic cation transporter 2; Organic cation transporter 3; Plasma membrane monoamine transporter; Polyspecific transporter