Organic Cation Transporters in Brain Histamine Clearance: Physiological and Psychiatric Implications

Fumito Naganuma, Takeo Yoshikawa

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)


Histamine acts as a neurotransmitter in the central nervous system and is involved in numerous physiological functions. Recent studies have identified the causative role of decreased histaminergic systems in various neurological disorders. Thus, the brain histamine system has attracted attention as a therapeutic target to improve brain function. Neurotransmitter clearance is one of the most important processes for the regulation of neuronal activity and is an essential target for diverse drugs. Our previous study has shown the importance of histamine N-methyltransferase for the inactivation of brain histamine and the intracellular localization of this enzyme; the study indicated that the transport system for the movement of positively charged histamine from the extracellular to intracellular space is a prerequisite for histamine inactivation. Several studies on in vitro astrocytic histamine transport have indicated the contribution of organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) in histamine uptake, although the importance of these transporters in in vivo histamine clearance remains unknown. Immunohistochemical analyses have revealed the expression of OCT3 and PMAT on neurons, emphasizing the importance of investigating neuronal histamine uptake. Further studies using knockout mice or fast-scan cyclic voltammetry will accelerate the research on histamine transporters. In this review article, we summarize histamine transport assays and describe the candidate transporters responsible for histamine transport in the brain.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer Science and Business Media Deutschland GmbH
Number of pages17
Publication statusPublished - 2021

Publication series

NameHandbook of Experimental Pharmacology
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325


  • Histamine
  • Histamine N-methyltransferase
  • Organic cation transporter
  • Plasma membrane monoamine transporter

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)


Dive into the research topics of 'Organic Cation Transporters in Brain Histamine Clearance: Physiological and Psychiatric Implications'. Together they form a unique fingerprint.

Cite this