H1受体是一种属于视紫红质样G蛋白偶联受体家族的受体,可被组胺激活。它在平滑肌、血管内皮细胞、心脏、中枢神经系统中表达。H1受体与细胞内Gα蛋白的Gαq亚基英语Gq_alpha_subunit连接,激活磷脂酶C肌醇三磷酸(IP3)信号通路。作用于该受体的抗组胺药被用作抗过敏药物。该受体的晶体结构已确定[6]并用于在基于结构的虚拟筛选研究中发现新的组胺H1受体配体[7]

HRH1
已知的结构
PDB直系同源搜索: PDBe RCSB
识别号
别名HRH1;, H1-R, H1R, HH1R, hisH1, histamine receptor H1
外部IDOMIM600167 MGI107619 HomoloGene668 GeneCardsHRH1
为以下药物的标靶
维拉佐酮、​2-吡啶乙胺、​组胺、​阿米替林、​阿立哌唑、​阿司咪唑、​氮䓬斯汀、​氯苯那敏、​氯丙嗪、​ciproxifan、​氯马斯汀、​clobenpropit、​氯氮平、​conessine、​赛克利嗪、​希普利敏、​地氯雷他定、​苯海拉明、​依匹斯汀、​非索非那定、​氟奋乃静、​fluspirilene、​氟哌啶醇、​羟嗪、​英普咪定、​酮替芬、​氯雷他定、​洛沙平、​MK-0249、​(±)-molindone、​奥氮平、​奋乃静、​匹莫齐特、​酰胺哌啶酮、​替洛利生、​盐酸异丙嗪、​喹硫平、​利培酮、​sertindole、​特非那定、​thioridazine、​(Z)-thiothixene、​三氟拉嗪、​tripelennamine、​triprolidine、​齐拉西酮、​zotepine、​ABT-239、​盐酸西替利嗪、​盐酸左西替利嗪、​pyrilamine[1]
基因位置(人类
3号染色体
染色体3号染色体[2]
3号染色体
HRH1的基因位置
HRH1的基因位置
基因座3p25.3起始11,137,093 bp[2]
终止11,263,557 bp[2]
RNA表达模式


查阅更多表达数据
直系同源
物种人类小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_000861
​NM_001098211
​NM_001098212
​NM_001098213

蛋白序列

NP_000852
​NP_001091681
​NP_001091682
​NP_001091683

基因位置​(UCSC)Chr 3: 11.14 – 11.26 MbChr 6: 114.37 – 114.46 Mb
PubMed​查找[4][5]
维基数据
查看/编辑人类查看/编辑小鼠

功能

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NF-κB(调节炎症过程的转录因子)的表达受到H1受体的固有活性英语Receptor_(biochemistry)#Constitutive_activity以及与受体结合的激动剂的促进。[8]抗组胺药已被证明可以减弱NF-κB的表达并减轻相关细胞中的某些炎症过程。[8]

组胺还可能在阴茎勃起中起作用。[9]

神经生物学

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组胺H1受体被内源性组胺激活,内源性组胺是由下丘脑结节乳状体中的神经元释放的。结节乳状体的组胺能神经元在“唤醒”周期中变得活跃,以大约2赫兹的频率放电;而在慢波睡眠期间,该放电频率降至大约0.5赫兹。[10]

结节乳状体是一种组胺能核,对调节睡眠-觉醒周期起重要作用。[11] 透过血脑屏障的H1拮抗剂可以抑制结节乳状体投射的神经元上的H1受体的活性,这种作用可能是这些药物造成嗜睡作用的原因。[来源请求]

参见

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参考文献

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  1. ^ 對H1組織胺受體起作用的藥物;在維基數據上查看/編輯參考. 
  2. ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000196639 - Ensembl, May 2017
  3. ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000053004 - Ensembl, May 2017
  4. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, et al. Structure of the human histamine H1 receptor complex with doxepin. Nature. June 2011, 475 (7354): 65–70. PMC 3131495 . PMID 21697825. doi:10.1038/nature10236. 
  7. ^ de Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, et al. Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor. Journal of Medicinal Chemistry. December 2011, 54 (23): 8195–8206. PMC 3228891 . PMID 22007643. doi:10.1021/jm2011589. 
  8. ^ 8.0 8.1 Canonica GW, Blaiss M. Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. The World Allergy Organization Journal. February 2011, 4 (2): 47–53. PMC 3500039 . PMID 23268457. doi:10.1097/WOX.0b013e3182093e19. The H1-receptor is a transmembrane protein belonging to the G-protein coupled receptor family. Signal transduction from the extracellular to the intracellular environment occurs as the GPCR becomes activated after binding of a specific ligand or agonist. A subunit of the G-protein subsequently dissociates and affects intracellular messaging including downstream signaling accomplished through various intermediaries such as cyclic AMP, cyclic GMP, calcium, and nuclear factor kappa B (NF-κB), a ubiquitous transcription factor thought to play an important role in immune-cell chemotaxis, proinflammatory cytokine production, expression of cell adhesion molecules, and other allergic and inflammatory conditions.1,8,12,30–32 ... For example, the H1-receptor promotes NF-κB in both a constitutive and agonist-dependent manner and all clinically available H1-antihistamines inhibit constitutive H1-receptor-mediated NF-κB production ...
    Importantly, because antihistamines can theoretically behave as inverse agonists or neutral antagonists, they are more properly described as H1-antihistamines rather than H1-receptor antagonists.15
     
  9. ^ Cará AM, Lopes-Martins RA, Antunes E, Nahoum CR, De Nucci G. The role of histamine in human penile erection. British Journal of Urology. February 1995, 75 (2): 220–224. PMID 7850330. doi:10.1111/j.1464-410x.1995.tb07315.x. 
  10. ^ Passani MB, Lin JS, Hancock A, Crochet S, Blandina P. The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders. Trends in Pharmacological Sciences. December 2004, 25 (12): 618–625. PMID 15530639. doi:10.1016/j.tips.2004.10.003. 
  11. ^ Malenka RC, Nestler EJ, Hyman SE. Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 175–176. ISBN 9780071481274. Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus.  ... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory ... It also appears that histamine is involved in the regulation of feeding and energy balance. 

延伸阅读

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外部链接

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  • Histamine Receptors: H1. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. [2023-12-15]. (原始内容存档于2016-03-03).