Error: Pathway image not found.
Histamine H1 Receptor Activation
Last Updated: 2019-09-15
Histamine is a ubiquitous messenger molecule released from mast cells, basophils, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3, and H4. Histamine receptor H1 belongs to the family of G-protein-coupled receptors (GPCRs), and it is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. It is linked to an intracellular G-protein (Gαq) that activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway which promotes inflammatory processes through calcium ion release and expression of the NF-κB immune response transcription factor. H1-antihistamines inactivate the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Upon binding by histamine, the H1 receptor allosterically activates the G-protein by exchanging GDP for GTP at the G-protein's alpha subunit (Gαq). This results in the dissociation of a Gαq-GTP monomer and a Gβγ dimer from the receptor . Gαq-GTP activates phospholipase C-beta which cleaves the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into the secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm to the ER and binds to the inositol 1,4,5-trisphosphate (Ins3P) receptor, releasing calcium from the endoplasmic reticulum into the cytoplasm. An increase in the calcium concentration results in increased mediator release and decreased mast cell stability. Both calcium and DAG activate the kinase activity of protein kinase C beta (PKC). Among many other functions, PKC activates NF-κB. This leads to increased antigen presentation and increased expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors.
Histamine H1 Receptor Activation References
Suh PG, Ryu SH, Moon KH, Suh HW, Rhee SG: Cloning and sequence of multiple forms of phospholipase C. Cell. 1988 Jul 15;54(2):161-9. doi: 10.1016/0092-8674(88)90548-x.Pubmed: 3390863
Jhon DY, Lee HH, Park D, Lee CW, Lee KH, Yoo OJ, Rhee SG: Cloning, sequencing, purification, and Gq-dependent activation of phospholipase C-beta 3. J Biol Chem. 1993 Mar 25;268(9):6654-61.Pubmed: 8454637
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.Pubmed: 22673903
Wang XB, Funada M, Imai Y, Revay RS, Ujike H, Vandenbergh DJ, Uhl GR: rGbeta1: a psychostimulant-regulated gene essential for establishing cocaine sensitization. J Neurosci. 1997 Aug 1;17(15):5993-6000.Pubmed: 9221795
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.Pubmed: 15489334
Ryba NJ, Tirindelli R: A novel GTP-binding protein gamma-subunit, G gamma 8, is expressed during neurogenesis in the olfactory and vomeronasal neuroepithelia. J Biol Chem. 1995 Mar 24;270(12):6757-67. doi: 10.1074/jbc.270.12.6757.Pubmed: 7896821
Fujimoto K, Horio Y, Sugama K, Ito S, Liu YQ, Fukui H: Genomic cloning of the rat histamine H1 receptor. Biochem Biophys Res Commun. 1993 Jan 15;190(1):294-301. doi: 10.1006/bbrc.1993.1045.Pubmed: 7678492
Lesch KP, Manji HK: Signal-transducing G proteins and antidepressant drugs: evidence for modulation of alpha subunit gene expression in rat brain. Biol Psychiatry. 1992 Oct 1;32(7):549-79. doi: 10.1016/0006-3223(92)90070-g.Pubmed: 1333286
Mignery GA, Newton CL, Archer BT 3rd, Sudhof TC: Structure and expression of the rat inositol 1,4,5-trisphosphate receptor. J Biol Chem. 1990 Jul 25;265(21):12679-85.Pubmed: 2165071
Danoff SK, Ferris CD, Donath C, Fischer GA, Munemitsu S, Ullrich A, Snyder SH, Ross CA: Inositol 1,4,5-trisphosphate receptors: distinct neuronal and nonneuronal forms derived by alternative splicing differ in phosphorylation. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2951-5. doi: 10.1073/pnas.88.7.2951.Pubmed: 1849282
Smutzer G, Zimmerman JE, Hahn CG, Ruscheinsky DD, Rodriguez A, Han LY, Arnold SE: Inositol 1,4,5-trisphosphate receptor expression in mammalian olfactory tissue. Brain Res Mol Brain Res. 1997 Mar;44(2):347-54. doi: 10.1016/s0169-328x(96)00282-3.Pubmed: 9073177
Knopf JL, Lee MH, Sultzman LA, Kriz RW, Loomis CR, Hewick RM, Bell RM: Cloning and expression of multiple protein kinase C cDNAs. Cell. 1986 Aug 15;46(4):491-502. doi: 10.1016/0092-8674(86)90874-3.Pubmed: 3755379
Ono Y, Kurokawa T, Fujii T, Kawahara K, Igarashi K, Kikkawa U, Ogita K, Nishizuka Y: Two types of complementary DNAs of rat brain protein kinase C. Heterogeneity determined by alternative splicing. FEBS Lett. 1986 Oct 6;206(2):347-52. doi: 10.1016/0014-5793(86)81010-9.Pubmed: 2428667
Housey GM, Johnson MD, Hsiao WL, O'Brian CA, Murphy JP, Kirschmeier P, Weinstein IB: Overproduction of protein kinase C causes disordered growth control in rat fibroblasts. Cell. 1988 Feb 12;52(3):343-54. doi: 10.1016/s0092-8674(88)80027-8.Pubmed: 3345563
Hamil KG, Hall SH: Cloning of rat Sertoli cell follicle-stimulating hormone primary response complementary deoxyribonucleic acid: regulation of TSC-22 gene expression. Endocrinology. 1994 Mar;134(3):1205-12. doi: 10.1210/endo.134.3.8161377.Pubmed: 8161377
This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0063452
Highlighted elements will appear in red.
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data