组胺H₁受体

HRH1
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	3RZE
识别号
别名	HRH1；, H1-R, H1R, HH1R, hisH1, histamine receptor H1
外部ID	OMIM：600167 MGI：107619 HomoloGene：668 GeneCards：HRH1
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
基因位置（人类）
染色体	3号染色体
终止	11,263,557 bp
基因位置（小鼠）
染色体	小鼠6号染色体
终止	114,460,257 bp
RNA表达模式
	; ;
	查阅更多表达数据
基因本体
分子功能	• histamine receptor activity; • signal transducer activity; • G protein-coupled receptor activity; • G protein-coupled serotonin receptor activity; • neurotransmitter receptor activity;
细胞组分	• integral component of membrane; • 膜; • integral component of plasma membrane; • 细胞膜; • 细胞质基质; • 树突;
生物学过程	• eosinophil chemotaxis; • inositol phosphate-mediated signaling; • regulation of vasoconstriction; • positive regulation of inositol trisphosphate biosynthetic process; • cellular response to histamine; • regulation of vascular permeability; • phospholipase C-activating G protein-coupled receptor signaling pathway; • regulation of synaptic plasticity; • G protein-coupled receptor signaling pathway; • modulation of chemical synaptic transmission; • inflammatory response; • visual learning; • 信号转导; • 记忆; • positive regulation of vasoconstriction; • G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; • 化学性突触传递; • G protein-coupled serotonin receptor signaling pathway;
	Sources:Amigo / QuickGO
直系同源
	3269
	15465
	ENSG00000196639
	ENSMUSG00000053004
	P35367
	P70174
	NM_000861; NM_001098211; NM_001098212; NM_001098213
NM_001252642; NM_001252643; NM_008285; NM_001317124; NM_001317125;
	NM_001317126
	NP_000852; NP_001091681; NP_001091682; NP_001091683
NP_001239571; NP_001239572; NP_001304053; NP_001304054; NP_001304055;
	NP_032311
	维基数据
查看/编辑人类	查看/编辑小鼠

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G_α蛋白的Gαq亚基（英语：Gq_alpha_subunit）连接，激活磷脂酶C和肌醇三磷酸（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]

功能

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

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

参考文献

^ 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.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000196639 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000053004 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ ^8.0 ^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
^ 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.
^ 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.
^ 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

Mitsuchashi M, Payan DG. Molecular and cellular analysis of histamine H1 receptors on cultured smooth muscle cells. Journal of Cellular Biochemistry. June 1989, 40 (2): 183–192. PMID 2670975. S2CID 43161416. doi:10.1002/jcb.240400207.
Braman SS. Histamine receptors in the lung. New England and Regional Allergy Proceedings. 1987, 8 (2): 116–120. PMID 2886904. doi:10.2500/108854187778994446.
Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, et al. International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacological Reviews. September 1997, 49 (3): 253–278. PMID 9311023.
Holden CA, Chan SC, Norris S, Hanifin JM. Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. Agents and Actions. October 1987, 22 (1–2): 36–42. PMID 2891264. S2CID 23962587. doi:10.1007/BF01968814.
Moguilevsky N, Varsalona F, Noyer M, Gillard M, Guillaume JP, Garcia L, et al. Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene. European Journal of Biochemistry. September 1994, 224 (2): 489–495. PMID 7925364. doi:10.1111/j.1432-1033.1994.00489.x  .
Fukui H, Fujimoto K, Mizuguchi H, Sakamoto K, Horio Y, Takai S, et al. Molecular cloning of the human histamine H1 receptor gene. Biochemical and Biophysical Research Communications. June 1994, 201 (2): 894–901. PMID 8003029. doi:10.1006/bbrc.1994.1786.
Le Coniat M, Traiffort E, Ruat M, Arrang JM, Berger R. Chromosomal localization of the human histamine H1-receptor gene. Human Genetics. August 1994, 94 (2): 186–188. PMID 8045566. S2CID 13583779. doi:10.1007/bf00202867.
De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, Luyten WH. Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor. Biochemical and Biophysical Research Communications. December 1993, 197 (3): 1601–1608. PMID 8280179. doi:10.1006/bbrc.1993.2662.
Hishinuma S, Young JM. Characteristics of the binding of [3H]-mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation. British Journal of Pharmacology. November 1995, 116 (6): 2715–2723. PMC 1909113  . PMID 8590995. doi:10.1111/j.1476-5381.1995.tb17232.x.
Max SI, Chowdhury BA, Fraser CM. Sequence analysis of the 5'-untranslated region of the human H1 histamine receptor-encoding gene. Gene. June 1996, 171 (2): 309–310. PMID 8666296. doi:10.1016/0378-1119(96)00036-4.
De Backer MD, Loonen I, Verhasselt P, Neefs JM, Luyten WH. Structure of the human histamine H1 receptor gene. The Biochemical Journal. November 1998, 335 (Pt 3): 663–670. PMC 1219830  . PMID 9794809. doi:10.1042/bj3350663.
Horváth BV, Szalai C, Mándi Y, László V, Radvány Z, Darvas Z, Falus A. Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets. Immunology Letters. November 1999, 70 (2): 95–99. PMID 10569698. doi:10.1016/S0165-2478(99)00126-1.
Wang KY, Arima N, Higuchi S, Shimajiri S, Tanimoto A, Murata Y, et al. Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages. FEBS Letters. May 2000, 473 (3): 345–348. PMID 10818238. S2CID 772640. doi:10.1016/S0014-5793(00)01560-X.
Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. The Journal of Biological Chemistry. November 2000, 275 (47): 36781–36786. PMID 10973974. doi:10.1074/jbc.M006480200  .
Brew OB, Sullivan MH. Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy. Inflammation Research. September 2001, 50 (9): 449–452. PMID 11603849. S2CID 28710647. doi:10.1007/PL00000269.
Gutzmer R, Langer K, Lisewski M, Mommert S, Rieckborn D, Kapp A, Werfel T. Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells. The Journal of Allergy and Clinical Immunology. March 2002, 109 (3): 524–531. PMID 11898002. doi:10.1067/mai.2002.121944.
Idzko M, la Sala A, Ferrari D, Panther E, Herouy Y, Dichmann S, et al. Expression and function of histamine receptors in human monocyte-derived dendritic cells. The Journal of Allergy and Clinical Immunology. May 2002, 109 (5): 839–846. PMID 11994709. doi:10.1067/mai.2002.124044.

外部链接

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）.

[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.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000196639 - Ensembl, May 2017

[refGRCm38Ensembl-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] 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.

[H1_receptor_NF-κB_signaling-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.

[pmid15530639-10] 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.

[Histamine_pathways-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.

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