组胺H₁受体

HRH1
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	3RZE
識別號
别名	HRH1；, H1-R, H1R, HH1R, hisH1, histamine receptor H1
外部ID	OMIM：600167 MGI：107619 HomoloGene：668 GeneCards：HRH1
為以下藥物的標靶
	维拉佐酮、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、匹莫齊特、酰胺哌啶酮、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、盐酸西替利嗪、鹽酸左西替利嗪、pyrilamine[1]
基因位置（人类）
染色体	3號染色體[2]
终止	11,263,557 bp[2]
基因位置（小鼠）
染色体	小鼠6号染色体[3]
终止	114,460,257 bp[3]
RNA表达模式
	; ;
	查阅更多表达数据
基因本體
分子功能	• histamine receptor activity; • signal transducer activity; • G protein-coupled receptor activity; • G protein-coupled serotonin receptor activity; • neurotransmitter receptor activity;
細胞組分	• integral component of membrane; • 膜; • integral component of plasma membrane; • 细胞膜; • 细胞质基质; • 树突;
生物學過程	• 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; • 訊息傳遞; • 記憶; • 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
	維基數據

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。

参见

抗组胺药：组胺受体的拮抗剂
H₁受体拮抗剂
组胺H₂受体
组胺H₃受体
组胺H₄受体

参考文献

.
GRCh38: Ensembl release 89: ENSG00000196639 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000053004 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. 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. . 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. . Journal of Medicinal Chemistry. December 2011, 54 (23): 8195–8206. PMC 3228891 . PMID 22007643. doi:10.1021/jm2011589.
Canonica GW, Blaiss M. . 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. . 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. . 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. . Sydor A, Brown RY (编). 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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Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, et al. . Pharmacological Reviews. September 1997, 49 (3): 253–278. PMID 9311023.
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Moguilevsky N, Varsalona F, Noyer M, Gillard M, Guillaume JP, Garcia L, et al. . 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. . Biochemical and Biophysical Research Communications. June 1994, 201 (2): 894–901. PMID 8003029. doi:10.1006/bbrc.1994.1786.
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De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, Luyten WH. . Biochemical and Biophysical Research Communications. December 1993, 197 (3): 1601–1608. PMID 8280179. doi:10.1006/bbrc.1993.2662.
Hishinuma S, Young JM. . 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. . 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. . The Biochemical Journal. November 1998, 335 (Pt 3): 663–670. PMC 1219830 . PMID 9794809. doi:10.1042/bj3350663.
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外部链接

. 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）.

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[1] .

[refGRCh38Ensembl-2] GRCh38: Ensembl release 89: ENSG00000196639 - Ensembl, May 2017

[refGRCm38Ensembl-3] GRCm38: Ensembl release 89: ENSMUSG00000053004 - Ensembl, May 2017

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] . 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. . 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. . Journal of Medicinal Chemistry. December 2011, 54 (23): 8195–8206. PMC 3228891 . PMID 22007643. doi:10.1021/jm2011589.

[H1_receptor_NF-κB_signaling-8] Canonica GW, Blaiss M. . 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. . 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. . 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. . Sydor A, Brown RY (编). 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.