H3 receptori funkcionišu kao presinaptički autoreceptori na histaminskim neuronima.[2]
Raznovrsnost izražavanja H3 receptora širom korteksa i podkorteksa je indikacija njegove sposobnosti da moduliše otpuštanje velikog broja neurotransmitera.
Postoji najmanje šest izoformi H3 receptora kod ljudi, i više od 20 je otkriveno do sada računajući druge vrste.[4] Kod pacova je do sad otkriveno šest podtipova H3 receptora, dok su kod miševa poznate tri.[5] Ti podtipovi imaju suptilne razlike u pogledu farmakologije (kao i distribucije, sudeći po istraživanjina na pacovima), ali njihove precizne fiziološke uloge nisu razjašnjene.
Farmakologija
Agonisti
Nisu poznati terapeutski proizvodi koji deluju kao selektivni agonisti za H3 receptore. Postoji nekoliko jedinjenja koja se koriste kao istraživačka oruđa koja su u znatnoj meri selektivni agonisti. Neka od njih su:
Cipralisant - Inicijalno istraživan kao H3 antagonist, ali je kasnije utvrđeno da je agonist, pokazuje funkcionalnu selektivnost. Aktivira deo G protein spregnutih puteva[6]
Ovaj receptor je predložen za biološki cilj u tretiranju poremećaja sna.[9] Takođe se smatra da modulacija dejstva ovog receptora može da nađe primenu u tretmanu neuropatičkog bola.[10]
↑Attoub S, Moizo L, Sobhani I, Laigneau JP, Lewin MJ, Bado A (June 2001). „The H3 receptor is involved in cholecystokinin inhibition of food intake in rats”. Life Sci.69 (4): 469–78. DOI:10.1016/S0024-3205(01)01138-9. PMID11459437.
↑Rouleau A, Héron A, Cochois V, Pillot C, Schwartz JC, Arrang JM (2004). „Cloning and expression of the mouse histamine H3 receptor: evidence for multiple isoforms”. J. Neurochem.90 (6): 1331–8. DOI:10.1111/j.1471-4159.2004.02606.x. PMID15341517.
↑Krueger KM, Witte DG, Ireland-Denny L, Miller TR, Baranowski JL, Buckner S, Milicic I, Esbenshade TA, Hancock AA. G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations. Journal of Pharmacology and Experimental Therapeutics. 2005 Jul;314(1):271-81. PMID15821027
↑Esbenshade TA, Fox GB, Krueger KM, Baranowski JL, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan JB, Faghih R, Bennani YL, Williams M, Hancock AA. Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist. Biochemical Pharmacology. 2004 September 1;68(5):933-45. PMID15294456
↑Passani MB, Lin JS, Hancock A, Crochet S, Blandina P (2004). „The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders”. Trends Pharmacol. Sci.25 (12): 618–25. DOI:10.1016/j.tips.2004.10.003. PMID15530639.
↑Medhurst SJ, Collins SD, Billinton A, Bingham S, Dalziel RG, Brass A, Roberts JC, Medhurst AD, Chessell IP (2008). „Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain.”. Pain138 (1): 61–78. DOI:10.1016/j.pain.2007.11.006. PMID18164820.
↑Leurs R, Bakker RA, Timmerman H, de Esch IJ (2005). „The histamine H3 receptor: from gene cloning to H3 receptor drugs”. Nature reviews. Drug discovery4 (2): 107–20. DOI:10.1038/nrd1631. PMID15665857.
↑Arrang JM, Garbarg M, Schwartz JC (1983). „Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor”. Nature302 (5911): 832–7. DOI:10.1038/302832a0. PMID6188956.
↑Toyota H, Dugovic C, Koehl M, Laposky AD, Weber C, Ngo K, Wu Y, Lee DH, Yanai K, Sakurai E, Watanabe T, Liu C, Chen J, Barbier AJ, Turek FW, Fung-Leung WP, Lovenberg TW (2002). „Behavioral characterization of mice lacking histamine H3 receptors”. Mol. Pharmacol.62 (2): 389–97. DOI:10.1124/mol.62.2.389. PMID12130692.
Literatura
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Malinowska B, Godlewski G, Schlicker E (1998). „Histamine H3 receptors--general characterization and their function in the cardiovascular system”. J. Physiol. Pharmacol.49 (2): 191–211. PMID9670104.
Leurs R, Bakker RA, Timmerman H, de Esch IJ (2005). „The histamine H3 receptor: from gene cloning to H3 receptor drugs”. Nature reviews. Drug discovery4 (2): 107–20. DOI:10.1038/nrd1631. PMID15665857.
Esbenshade TA, Fox GB, Cowart MD (2006). „Histamine H3 receptor antagonists: preclinical promise for treating obesity and cognitive disorders”. Mol. Interv.6 (2): 77–88, 59. DOI:10.1124/mi.6.2.5. PMID16565470.
Lovenberg TW, Roland BL, Wilson SJ, et al. (1999). „Cloning and functional expression of the human histamine H3 receptor”. Mol. Pharmacol.55 (6): 1101–7. PMID10347254.
Nakamura T, Itadani H, Hidaka Y, et al. (2001). „Molecular cloning and characterization of a new human histamine receptor, HH4R”. Biochem. Biophys. Res. Commun.279 (2): 615–20. DOI:10.1006/bbrc.2000.4008. PMID11118334.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). „The DNA sequence and comparative analysis of human chromosome 20”. Nature414 (6866): 865–71. DOI:10.1038/414865a. PMID11780052.
Wiedemann P, Bönisch H, Oerters F, Brüss M (2002). „Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations”. Journal of neural transmission (Vienna, Austria : 1996)109 (4): 443–53. DOI:10.1007/s007020200036. PMID11956964.
Lozeva V, Tuomisto L, Tarhanen J, Butterworth RF (2004). „Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma”. J. Hepatol.39 (4): 522–7. DOI:10.1016/S0168-8278(03)00353-2. PMID12971961.
„Histamine Receptors: H3”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2013-12-25.