Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Carbinoxamine H1 Antihistamine Smooth Muscle Relaxation Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-12-19
Last Updated: 2024-01-15
Carbinoxamine is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles.
H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Carbinoxamine also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.
References
Carbinoxamine H1 Antihistamine Smooth Muscle Relaxation Pathway 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
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.
Pubmed: 17139284
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.
Pubmed: 17016423
Dorsch W, Hintschich C, Neuhauser J, Weber J: Sequential histamine inhalations cause increased bronchial histamine reactivity in guinea pigs: role of platelets, thromboxanes and prostacyclin. Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):148-55. doi: 10.1007/BF00500910.
Pubmed: 6387510
Wawrzynczak EJ, Perham RN: Isolation and nucleotide sequence of a cDNA encoding human calmodulin. Biochem Int. 1984 Aug;9(2):177-85.
Pubmed: 6385987
Rhyner JA, Ottiger M, Wicki R, Greenwood TM, Strehler EE: Structure of the human CALM1 calmodulin gene and identification of two CALM1-related pseudogenes CALM1P1 and CALM1P2. Eur J Biochem. 1994 Oct 1;225(1):71-82. doi: 10.1111/j.1432-1033.1994.00071.x.
Pubmed: 7925473
Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. doi: 10.1038/nature01348. Epub 2003 Jan 1.
Pubmed: 12508121
Kurabayashi M, Komuro I, Tsuchimochi H, Takaku F, Yazaki Y: Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones. J Biol Chem. 1988 Sep 25;263(27):13930-6.
Pubmed: 3417683
Hoffmann E, Shi QW, Floroff M, Mickle DA, Wu TW, Olley PM, Jackowski G: Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1. Nucleic Acids Res. 1988 Mar 25;16(5):2353. doi: 10.1093/nar/16.5.2353.
Pubmed: 3357795
Fodor WL, Darras B, Seharaseyon J, Falkenthal S, Francke U, Vanin EF: Human ventricular/slow twitch myosin alkali light chain gene characterization, sequence, and chromosomal location. J Biol Chem. 1989 Feb 5;264(4):2143-9.
Pubmed: 2789520
Caricasole A, Sala C, Roncarati R, Formenti E, Terstappen GC: Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1). Biochim Biophys Acta. 2000 Dec 15;1517(1):63-72. doi: 10.1016/s0167-4781(00)00260-8.
Pubmed: 11118617
Peruzzi D, Calabrese G, Faenza I, Manzoli L, Matteucci A, Gianfrancesco F, Billi AM, Stuppia L, Palka G, Cocco L: Identification and chromosomal localisation by fluorescence in situ hybridisation of human gene of phosphoinositide-specific phospholipase C beta(1). Biochim Biophys Acta. 2000 Apr 12;1484(2-3):175-82. doi: 10.1016/s1388-1981(00)00012-3.
Pubmed: 10760467
Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Feb 28;5(1):31-9. doi: 10.1093/dnares/5.1.31.
Pubmed: 9628581
Lazar V, Garcia JG: A single human myosin light chain kinase gene (MLCK; MYLK). Genomics. 1999 Apr 15;57(2):256-67.
Pubmed: 10198165
Potier MC, Chelot E, Pekarsky Y, Gardiner K, Rossier J, Turnell WG: The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3qcen-q21. Genomics. 1995 Oct 10;29(3):562-70. doi: 10.1006/geno.1995.9965.
Pubmed: 8575746
Garcia JG, Lazar V, Gilbert-McClain LI, Gallagher PJ, Verin AD: Myosin light chain kinase in endothelium: molecular cloning and regulation. Am J Respir Cell Mol Biol. 1997 May;16(5):489-94. doi: 10.1165/ajrcmb.16.5.9160829.
Pubmed: 9160829
Denier C, Ducros A, Durr A, Eymard B, Chassande B, Tournier-Lasserve E: Missense CACNA1A mutation causing episodic ataxia type 2. Arch Neurol. 2001 Feb;58(2):292-5. doi: 10.1001/archneur.58.2.292.
Pubmed: 11176968
Hans M, Urrutia A, Deal C, Brust PF, Stauderman K, Ellis SB, Harpold MM, Johnson EC, Williams ME: Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels. Biophys J. 1999 Mar;76(3):1384-400. doi: 10.1016/S0006-3495(99)77300-5.
Pubmed: 10049321
Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJ, Hofker MH, Ferrari MD, Frants RR: Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996 Nov 1;87(3):543-52. doi: 10.1016/s0092-8674(00)81373-2.
Pubmed: 8898206
Powers PA, Liu S, Hogan K, Gregg RG: Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent calcium channels are encoded by a single gene. J Biol Chem. 1992 Nov 15;267(32):22967-72.
Pubmed: 1385409
Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM: Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992 Jan;8(1):71-84. doi: 10.1016/0896-6273(92)90109-q.
Pubmed: 1309651
Collin T, Wang JJ, Nargeot J, Schwartz A: Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel beta subunit from normal human heart. Circ Res. 1993 Jun;72(6):1337-44. doi: 10.1161/01.res.72.6.1337.
Pubmed: 7916667
Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F: Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci. 1999 Jan 15;19(2):684-91.
Pubmed: 9880589
Gao B, Sekido Y, Maximov A, Saad M, Forgacs E, Latif F, Wei MH, Lerman M, Lee JH, Perez-Reyes E, Bezprozvanny I, Minna JD: Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). J Biol Chem. 2000 Apr 21;275(16):12237-42. doi: 10.1074/jbc.275.16.12237.
Pubmed: 10766861
Hobom M, Dai S, Marais E, Lacinova L, Hofmann F, Klugbauer N: Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit. Eur J Neurosci. 2000 Apr;12(4):1217-26. doi: 10.1046/j.1460-9568.2000.01009.x.
Pubmed: 10762351
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