Abstract
Histamine acts as a neurotransmitter to regulate various physiological functions in CNS. Recent reports showed the involvement of histaminergic dysfunction in neurological disorders. Neurotransmitter clearance is essential to determine brain neurotransmitter concentration. However, molecular mechanism of brain histamine clearance remains largely unknown. First, we examined the molecular mechanism of histamine clearance in primary human astrocytes. We demonstrated that extracellular histamine was transported through organic cation transporter (OCT) 3 and plasma membrane monoamine transporter (PMAT), and subsequently intracellular histamine was inactivated by histamine N-methyltransferase (HNMT) in cytosol. Next, we generated HNMT knockout (HNMT KO) mice to investigate the role of HNMT in vivo. HNMT deficiency dramatically enhanced brain histamine concentration, indicating the important role of HNMT in histamine inactivation. HNMT KO mice showed high aggression via abnormal histamine H2 receptor (H2R) activation and the disrupted sleep-wake cycle via excessive H1R activation. These observations show that HNMT plays a pivotal role in regulating brain histamine concentration, and modulates aggression as well as the sleep-wake cycle...Continue Reading
References
Apr 28, 1983·Nature·J M ArrangJ C Schwartz
Sep 9, 1983·Neuroscience Letters·T WatanabeH Wada
Feb 12, 1998·Naunyn-Schmiedeberg's Archives of Pharmacology·Z HusztiA Philippu
Aug 25, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Paul J GasserMiles Orchinik
Dec 31, 1910·The Journal of Physiology·H H Dale, P P Laidlaw
Jul 16, 2008·Physiological Reviews·Helmut L HaasOliver Selbach
Nov 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicole L BaganzLynette C Daws
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mei CuiKim Tieu
Jun 17, 2010·The American Journal of Psychiatry·Jim StevensonJohn O Warner
Sep 25, 2010·The Journal of Pharmacology and Experimental Therapeutics·Jorge D BrioniMarlon D Cowart
Jun 29, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Pengxiang ZhuMasahiro Sakanaka
Aug 23, 2012·Experimental Gerontology·Ling ShanAi-Min Bao
Mar 19, 2013·Glia·Takeo YoshikawaKazuhiko Yanai
Jan 15, 2014·Neuron·Lissandra Castellan BaldanChristopher Pittenger
Jul 25, 2014·The Journal of Nutrition·Takeo YoshikawaKazuhiko Yanai
Jan 1, 2014·Molecular Autism·Dea AdamsenBeat Thöny
Jul 25, 2015·Human Molecular Genetics·Abolfazl HeidariJohn B Vincent
Oct 28, 2015·ACS Chemical Neuroscience·Friederike MatthaeusThorsten Lau
Sep 30, 2016·Handbook of Experimental Pharmacology·Takeo Yoshikawa, Kazuhiko Yanai
Jan 29, 2017·Lancet Neurology·Zoltan SzakacsUNKNOWN HARMONY-CTP study group
Feb 9, 2017·FEBS Open Bio·Yamato MiuraKazuhiko Yanai
May 2, 2017·Pharmacology & Therapeutics·Kazuhiko YanaiManabu Tashiro
Nov 23, 2017·Scientific Reports·Fumito NaganumaKazuhiko Yanai