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Organic Cation Transporters in the Central Nervous System pp 169–185Cite as

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

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 266))

Abstract

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.

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Acknowledgements

This work was supported by Grant-in-Aid for Scientific Research (C) JP 18 K06886 to TY from the Japan Society for The Promotion of Science (JSPS) and by Grant-in-Aid for Young Scientists JP19K16296 to FN from JSPS.

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Authors and Affiliations

  1. Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Fumito Naganuma & Takeo Yoshikawa

  2. Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

    Fumito Naganuma

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  1. Fumito Naganuma
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  2. Takeo Yoshikawa
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Correspondence to Takeo Yoshikawa .

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Editors and Affiliations

  1. Departments of Cellular and Integrative Physiology, and Pharmacology, University of Texas Health Science Center, San Antonio, TX, USA

    Lynette C. Daws

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Naganuma, F., Yoshikawa, T. (2021). Organic Cation Transporters in Brain Histamine Clearance: Physiological and Psychiatric Implications. In: Daws, L.C. (eds) Organic Cation Transporters in the Central Nervous System. Handbook of Experimental Pharmacology, vol 266. Springer, Cham. https://doi.org/10.1007/164_2021_447

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