گیرنده اچ ۱ هیستامین

HRH1
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	3RZE
معین‌کننده‌ها
نام‌های دیگر	HRH1, H1-R, H1R, HH1R, hisH1, histamine receptor H1
شناسه‌های بیرونی	OMIM: 600167 MGI: 107619 HomoloGene: 668 GeneCards: HRH1
موقعیت ژن (موش)
کروموزوم	کروموزوم ۶ (موش)
پایان	114,460,257 bp
الگوی گسترش RNA
	; ;
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• histamine receptor activity; • signal transducer activity; • G protein-coupled receptor activity; • G protein-coupled serotonin receptor activity; • neurotransmitter receptor activity;
ترکیبات سلولی	• integral component of membrane; • membrane; • integral component of plasma membrane; • پوسته یاخته; • سیتوزول; • دندریت;
فرایند زیستی	• 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; • یادگیری بصری; • GO:0072468 ورارسانی پیام; • حافظه; • positive regulation of vasoconstriction; • G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; • chemical synaptic transmission; • G protein-coupled serotonin receptor signaling pathway;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	3269
	15465
	ENSG00000196639
	ENSMUSG00000053004
	P35367
	P70174
	NM_001098211، NM_001098212، NM_001098213 NM_000861، NM_001098211، NM_001098212، NM_001098213
	NM_001252643، NM_008285، NM_001317124، NM_001317125، NM_001317126، XM_030255192 NM_001252642، NM_001252643، NM_008285، NM_001317124، NM_001317125، NM_001317126، XM_030255192
	NP_001091681، NP_001091682، NP_001091683 NP_000852، NP_001091681، NP_001091682، NP_001091683
	NP_001239572، NP_001304053، NP_001304054، NP_001304055، NP_032311، XP_030111052 NP_001239571، NP_001239572، NP_001304053، NP_001304054، NP_001304055، NP_032311، XP_030111052
	مشاهده/ویرایش موش

گیرنده اچ ۱ هیستامین (انگلیسی: Histamine H1 receptor) یک گیرنده هیستامین متعلق به خانوادهٔ گیرنده‌های شبه‌رودوپسین جفت‌شونده با پروتئین جی است که با اتصال به هیستامین فعال می‌شود. این گیرنده در ماهیچه صاف، لایه درون‌رگی، قلب و دستگاه عصبی مرکزی یافت می‌شود.

گیرنده اچ ۱ هیستامین به یک جی‌پروتئین داخل‌سلولی (Gq) متصل شده و سبب فعال شدنِ مسیر پیام‌رسانی فسفولیپاز سی و اینوزیتول تری‌فسفات (IP3) می‌گردد. اثر ضد آلرژی داروهای آنتی‌هیستامین از طریق اثر بر این گیرنده حاصل می‌شود. پژوهش‌گران موفق شده‌اند ساختار کریستالی این گیرنده را شناسایی کنند (تصویر سمت چپ را ببینید) و از آن طریق، به کشف لیگاندهای جدید گیرنده‌های اچ ۱ هیستامین بپردازند.

نقش در التهاب

بیان فاکتور رونویسی «NF-κB» که فرایندهای التهابی را تنظیم می‌کند در اثر فعال شدنِ این گیرنده و همچنین با اتصال آگونیست‌های آن افزایش می‌یابد. داروهای آنتی‌هیستامین با فرونشانی و کاهش بیان ژنی NF-κB فرایند التهاب را در سلول‌های مربوط کاهش می‌دهند.

سروتونین مغز از فیبرهای عصبی موجود در هستهٔ تکمه‌ای‌پستانکی (tuberomammillary nucleus) در هیپوتالاموس ترشح می‌شوند که در ساعات بیداری انسان فعال هستند. فعالیت این فیبرهای عصبی هنگام خواب عمیق به‌شدت کاهش یافته و در مرحله خواب REM کاملاً متوقف می‌شود. از میان تمامی رشته‌های عصبی شناخته‌شده، این رشته‌های هیستامین‌ساز از همه بیشتر، «بیداری‌انتخاب» (wake-selective firing pattern) هستند. هسته تکمه‌ای‌پستانکی نقش بسیار مهمی در تنظیم چرخهٔ خواب-بیداری دارد. داروهای آنتی‌هیستامین می‌توانند از سد خونی مغزی عبور کرده و گیرنده اچ ۱ هیستامین را در مغز مهار کنند.

جستارهای وابسته

آنتی‌هیستامین

منابع

↑ 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, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (Jul 2011). "Structure of the human histamine H1 receptor complex with doxepin". Nature. 475 (7354): 65–70. doi:10.1038/nature10236. PMC 3131495. PMID 21697825.
↑ de Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, Iwata S, Shimamura T, Stevens RC, de Esch IJ, Leurs R (Dec 2011). "Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor". Journal of Medicinal Chemistry. 54 (23): 8195–206. doi:10.1021/jm2011589. PMC 3228891. PMID 22007643.
↑ Canonica GW, Blaiss M (Feb 2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". The World Allergy Organization Journal. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC 3500039. PMID 23268457. 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
↑ Passani MB, Lin JS, Hancock A, Crochet S, Blandina P (Dec 2004). "The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders". Trends in Pharmacological Sciences. 25 (12): 618–25. doi:10.1016/j.tips.2004.10.003. PMID 15530639.
↑ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 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.

برای مطالعهٔ بیشتر

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Braman SS (1987). "Histamine receptors in the lung". New England and Regional Allergy Proceedings. 8 (2): 116–20. doi:10.2500/108854187778994446. PMID 2886904.
Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL (Sep 1997). "International Union of Pharmacology. XIII. Classification of histamine receptors". Pharmacological Reviews. 49 (3): 253–78. PMID 9311023.
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Moguilevsky N, Varsalona F, Noyer M, Gillard M, Guillaume JP, Garcia L, Szpirer C, Szpirer J, Bollen A (Sep 1994). "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 / FEBS. 224 (2): 489–95. doi:10.1111/j.1432-1033.1994.00489.x. PMID 7925364.
Fukui H, Fujimoto K, Mizuguchi H, Sakamoto K, Horio Y, Takai S, Yamada K, Ito S (Jun 1994). "Molecular cloning of the human histamine H1 receptor gene". Biochemical and Biophysical Research Communications. 201 (2): 894–901. doi:10.1006/bbrc.1994.1786. PMID 8003029.
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[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000053004 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (Jul 2011). "Structure of the human histamine H1 receptor complex with doxepin". Nature. 475 (7354): 65–70. doi:10.1038/nature10236. PMC 3131495. PMID 21697825.

[5] Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, Iwata S, Shimamura T, Stevens RC, de Esch IJ, Leurs R (Dec 2011). "Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor". Journal of Medicinal Chemistry. 54 (23): 8195–206. doi:10.1021/jm2011589. PMC 3228891. PMID 22007643.

[H1_receptor_NF-κB_signaling-6] Canonica GW, Blaiss M (Feb 2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". The World Allergy Organization Journal. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC 3500039. PMID 23268457. 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

[pmid15530639-7] Passani MB, Lin JS, Hancock A, Crochet S, Blandina P (Dec 2004). "The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders". Trends in Pharmacological Sciences. 25 (12): 618–25. doi:10.1016/j.tips.2004.10.003. PMID 15530639.

[Histamine_pathways-8] Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 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.