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组胺H1受体

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維基百科,自由的百科全書
HRH1
已知的結構
PDB直系同源搜尋: PDBe RCSB
識別號
別名HRH1;, H1-R, H1R, HH1R, hisH1, histamine receptor H1
外部IDOMIM600167 MGI107619 HomoloGene668 GeneCardsHRH1
為以下藥物的標靶
維拉佐酮、​2-吡啶乙胺、​組織胺、​阿米替林、​阿立哌唑、​阿司咪唑、​氮䓬斯汀、​氯苯那敏、​氯丙嗪、​ciproxifan、​氯馬斯汀、​clobenpropit、​氯氮平、​conessine、​賽克利嗪、​希普利敏、​地氯雷他定、​苯海拉明、​依匹斯汀、​非索非那定、​氟奮乃靜、​fluspirilene、​氟哌啶醇、​羥嗪、​英普咪定、​酮替芬、​氯雷他定、​洛沙平、​MK-0249、​(±)-molindone、​奧氮平、​奮乃靜、​匹莫齊特、​醯胺哌啶酮、​替洛利生、​鹽酸異丙嗪、​喹硫平、​利培酮、​sertindole、​特非那定、​thioridazine、​(Z)-thiothixene、​三氟拉嗪、​tripelennamine、​triprolidine、​齊拉西酮、​zotepine、​ABT-239、​鹽酸西替利嗪、​鹽酸左西替利嗪、​pyrilamine[1]
基因位置(人類
3號染色體
染色體3號染色體[2]
3號染色體
HRH1的基因位置
HRH1的基因位置
基因座3p25.3起始11,137,093 bp[2]
終止11,263,557 bp[2]
RNA表現模式


查閱更多表現資料
直系同源
物種人類小鼠
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]
維基資料
檢視/編輯人類檢視/編輯小鼠

H1受體是一種屬於視紫紅質樣G蛋白偶聯受體家族的受體,可被組織胺活化。它在平滑肌、血管內皮細胞、心臟、中樞神經系統中表現。H1受體與細胞內Gα蛋白的Gαq亞基英語Gq_alpha_subunit連接,活化磷脂酶C肌醇三磷酸(IP3)信號通路。作用於該受體的抗組織胺藥被用作抗過敏藥物。該受體的晶體結構已確定[6]並用於在基於結構的虛擬篩選研究中發現新的組織胺H1受體配體[7]

功能

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NF-κB(調節發炎過程的轉錄因子)的表現受到H1受體的固有活性英語Receptor_(biochemistry)#Constitutive_activity以及與受體結合的促效劑的促進。[8]抗組織胺藥已被證明可以減弱NF-κB的表現並減輕相關細胞中的某些發炎過程。[8]

組織胺還可能在陰莖勃起中起作用。[9]

神經生物學

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組織胺H1受體被內源性組織胺活化,內源性組織胺是由下視丘結節乳狀體中的神經元釋放的。結節乳狀體的組織胺能神經元在「喚醒」周期中變得活躍,以大約2赫茲的頻率放電;而在慢波睡眠期間,該放電頻率降至大約0.5赫茲。[10]

結節乳狀體是一種組織胺能核,對調節睡眠-覺醒周期起重要作用。[11] 透過血腦屏障的H1拮抗劑可以抑制結節乳狀體投射的神經元上的H1受體的活性,這種作用可能是這些藥物造成嗜睡作用的原因。[來源請求]

參見

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參考文獻

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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可免費查閱. 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可免費查閱. 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可免費查閱. 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 (編). 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. 

延伸閱讀

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外部連結

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  • Histamine Receptors: H1. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. [2023-12-15]. (原始內容存檔於2016-03-03).