Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Gq Histaminic Smooth Muscle Contraction
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2023-09-05
Last Updated: 2023-11-27
The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Histamine H1 receptors are activated by endogenous histamine, which is released by neurons that have their cell bodies in the tuberomammillary nucleus of the hypothalamus. Gq protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gq/11 (Gq/G11) family or Gq/11/14/15 family to include closely related family members. G alpha subunits may be referred to as Gq alpha, Gαq, or Gqα. Gq proteins couple to G protein-coupled receptors to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 acts as a second messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC). The general function of Gq is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα protein such as Gαq, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex. When not stimulated by a receptor, Gα is bound to guanosine diphosphate (GDP) and to Gβγ to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a hormone or neurotransmitter), the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and guanosine triphosphate (GTP) binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ. Gq/11/14/15 proteins all activate beta-type phospholipase C (PLC-β) to signal through calcium and PKC signaling pathways. PLC-β then cleaves a specific plasma membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG remains bound to the membrane, and IP3 is released as a soluble molecule into the cytoplasm. IP3 diffuses to bind to IP3 receptors, a specialized calcium channel in the endoplasmic reticulum (ER). These channels are specific to calcium and only allow the passage of calcium from the ER into the cytoplasm. Since cells actively sequester calcium in the ER to keep cytoplasmic levels low, this release causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity through calcium binding proteins and calcium-sensitive processes. The functions of H1 activating the Gq signalling cascade in smooth muscle include ileum contraction and bronchoconstriction mainly.
References
Gq Histaminic Smooth Muscle Contraction References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615-49. doi: 10.1146/annurev.bi.56.070187.003151.
Pubmed: 3113327
Rodbell M: Nobel Lecture. Signal transduction: evolution of an idea. Biosci Rep. 1995 Jun;15(3):117-33. doi: 10.1007/BF01207453.
Pubmed: 7579038
Ichimura K, Jackson RT: H1 and H2 histamine receptors in the in vitro nasal mucosa. Acta Otolaryngol. 1985 May-Jun;99(5-6):610-9. doi: 10.3109/00016488509182268.
Pubmed: 4024912
Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL: International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev. 1997 Sep;49(3):253-78.
Pubmed: 9311023
McNally EM, Buttrick PM, Leinwand LA: Ventricular myosin light chain 1 is developmentally regulated and does not change in hypertension. Nucleic Acids Res. 1989 Apr 11;17(7):2753-67. doi: 10.1093/nar/17.7.2753.
Pubmed: 2717409
Periasamy M, Wadgaonkar R, Kumar C, Martin BJ, Siddiqui MA: Characterization of a rat myosin alkali light chain gene expressed in ventricular and slow twitch skeletal muscles. Nucleic Acids Res. 1989 Oct 11;17(19):7723-34. doi: 10.1093/nar/17.19.7723.
Pubmed: 2798124
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
Roush CL, Kennelly PJ, Glaccum MB, Helfman DM, Scott JD, Krebs EG: Isolation of the cDNA encoding rat skeletal muscle myosin light chain kinase. Sequence and tissue distribution. J Biol Chem. 1988 Jul 25;263(21):10510-6.
Pubmed: 2839493
Herring BP, Nunnally MH, Gallagher PJ, Stull JT: Molecular characterization of rat skeletal muscle myosin light chain kinase. Am J Physiol. 1989 Feb;256(2 Pt 1):C399-404. doi: 10.1152/ajpcell.1989.256.2.C399.
Pubmed: 2465691
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
Sherbany AA, Parent AS, Brosius J: Rat calmodulin cDNA. DNA. 1987 Jun;6(3):267-72. doi: 10.1089/dna.1987.6.267.
Pubmed: 2885164
Nojima H: Structural organization of multiple rat calmodulin genes. J Mol Biol. 1989 Jul 20;208(2):269-82. doi: 10.1016/0022-2836(89)90388-4.
Pubmed: 2527998
Jones DT, Reed RR: Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987 Oct 15;262(29):14241-9.
Pubmed: 2820999
De Vries L, Fischer T, Tronchere H, Brothers GM, Strockbine B, Siderovski DP, Farquhar MG: Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14364-9. doi: 10.1073/pnas.97.26.14364.
Pubmed: 11121039
Kimple RJ, De Vries L, Tronchere H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP: RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. J Biol Chem. 2001 Aug 3;276(31):29275-81. doi: 10.1074/jbc.M103208200. Epub 2001 May 31.
Pubmed: 11387333
Petrovski S, Kury S, Myers CT, Anyane-Yeboa K, Cogne B, Bialer M, Xia F, Hemati P, Riviello J, Mehaffey M, Besnard T, Becraft E, Wadley A, Politi AR, Colombo S, Zhu X, Ren Z, Andrews I, Dudding-Byth T, Schneider AL, Wallace G, Rosen ABI, Schelley S, Enns GM, Corre P, Dalton J, Mercier S, Latypova X, Schmitt S, Guzman E, Moore C, Bier L, Heinzen EL, Karachunski P, Shur N, Grebe T, Basinger A, Nguyen JM, Bezieau S, Wierenga K, Bernstein JA, Scheffer IE, Rosenfeld JA, Mefford HC, Isidor B, Goldstein DB: Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures. Am J Hum Genet. 2016 May 5;98(5):1001-1010. doi: 10.1016/j.ajhg.2016.03.011. Epub 2016 Apr 21.
Pubmed: 27108799
Steinrucke S, Lohmann K, Domingo A, Rolfs A, Baumer T, Spiegler J, Hartmann C, Munchau A: Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability. Neurol Genet. 2016 Sep 13;2(5):e106. doi: 10.1212/NXG.0000000000000106. eCollection 2016 Oct.
Pubmed: 27668284
Lohmann K, Masuho I, Patil DN, Baumann H, Hebert E, Steinrucke S, Trujillano D, Skamangas NK, Dobricic V, Huning I, Gillessen-Kaesbach G, Westenberger A, Savic-Pavicevic D, Munchau A, Oprea G, Klein C, Rolfs A, Martemyanov KA: Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans. Hum Mol Genet. 2017 Mar 15;26(6):1078-1086. doi: 10.1093/hmg/ddx018.
Pubmed: 28087732
Modarressi MH, Taylor KE, Wolfe J: Cloning, characterization, and mapping of the gene encoding the human G protein gamma 2 subunit. Biochem Biophys Res Commun. 2000 Jun 7;272(2):610-5. doi: 10.1006/bbrc.2000.2832.
Pubmed: 10833460
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. doi: 10.1186/1471-2164-8-399.
Pubmed: 17974005
Mattera R, Codina J, Crozat A, Kidd V, Woo SL, Birnbaumer L: Identification by molecular cloning of two forms of the alpha-subunit of the human liver stimulatory (GS) regulatory component of adenylyl cyclase. FEBS Lett. 1986 Sep 29;206(1):36-42. doi: 10.1016/0014-5793(86)81336-9.
Pubmed: 3093273
Harris BA: Complete cDNA sequence of a human stimulatory GTP-binding protein alpha subunit. Nucleic Acids Res. 1988 Apr 25;16(8):3585. doi: 10.1093/nar/16.8.3585.
Pubmed: 3131741
Kozasa T, Itoh H, Tsukamoto T, Kaziro Y: Isolation and characterization of the human Gs alpha gene. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2081-5. doi: 10.1073/pnas.85.7.2081.
Pubmed: 3127824
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 SMP0126962
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
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
Downloads
Settings