Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Dobutamine Action Pathway (New)
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2021-01-23
Last Updated: 2023-10-25
Dobutamine is a direct-acting sympathomimetic with a catecholamine-like structure akin to dopamine that is typically administered as intravenous medication. Unlike dopamine, dobutamine does not cause release of endogenous norepinephrine. Instead, it acts as a cardiac stimulant and stimulates adrenergic receptors to increase force of contraction. In the heart, its inotropic effect (increased contractility) is greater than its chronotropic effect, so dobutamine is used for acute heart failure and cardiogenic shock without evoking vasoconstriction or tachycardia. Dobutamine agonizes cardiac beta-1 adrenoceptors to increase intracellular via G protein-mediated cyclic AMP and protein kinase A (PKA) signaling, which increases calcium ion influx in cardiac myocytes from both intracellular stores and through L-type calcium channels. Dobutamine can also bind to beta-2 or alpha receptors, though less potently than it binds to beta-1 adrenoceptors. Through beta-2 adrenoceptor agonism, dobutamine may produce weak bronchodilation. For patients with cardiac decompensation, dobutamine is required for inotropic support. It may also function as a cardiotonic after myocardial infarction or open heart surgery. Clinically, it is used to induce cardiac stimulation with mild vasodilation. Overall, it exerts mild chronotropic, arrhythmogenic, hypertensive, and vasodilatory effects.
References
Dobutamine Pathway (New) References
Vallet B, Dupuis B, Chopin C: [Dobutamine: mechanisms of action and use in acute cardiovascular pathology]. Ann Cardiol Angeiol (Paris). 1991 Jun;40(6):397-402.
Pubmed: 1859148
Williams RS, Bishop T: Selectivity of dobutamine for adrenergic receptor subtypes: in vitro analysis by radioligand binding. J Clin Invest. 1981 Jun;67(6):1703-11. doi: 10.1172/jci110208.
Pubmed: 6263950
Romantowski J, Janowiak P, Wabich E, Kuziemski K: The impact of intravenous dobutamine on spirometry with bronchodilator test. Respir Med Case Rep. 2020 Oct 15;31:101264. doi: 10.1016/j.rmcr.2020.101264. eCollection 2020.
Pubmed: 33101902
Dubin A, Lattanzio B, Gatti L: The spectrum of cardiovascular effects of dobutamine - from healthy subjects to septic shock patients. Rev Bras Ter Intensiva. 2017 Oct-Dec;29(4):490-498. doi: 10.5935/0103-507X.20170068.
Pubmed: 29340539
Irannejad R, Pessino V, Mika D, Huang B, Wedegaertner PB, Conti M, von Zastrow M: Functional selectivity of GPCR-directed drug action through location bias. Nat Chem Biol. 2017 Jul;13(7):799-806. doi: 10.1038/nchembio.2389. Epub 2017 May 29.
Pubmed: 28553949
Ruffolo RR Jr: The pharmacology of dobutamine. Am J Med Sci. 1987 Oct;294(4):244-8. doi: 10.1097/00000441-198710000-00005.
Pubmed: 3310640
Tibayan FA, Chesnutt AN, Folkesson HG, Eandi J, Matthay MA: Dobutamine increases alveolar liquid clearance in ventilated rats by beta-2 receptor stimulation. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):438-44. doi: 10.1164/ajrccm.156.2.9609141.
Pubmed: 9279221
Sakuntabhai A, Burge S, Monk S, Hovnanian A: Spectrum of novel ATP2A2 mutations in patients with Darier's disease. Hum Mol Genet. 1999 Sep;8(9):1611-9. doi: 10.1093/hmg/8.9.1611.
Pubmed: 10441323
Ruiz-Perez VL, Carter SA, Healy E, Todd C, Rees JL, Steijlen PM, Carmichael AJ, Lewis HM, Hohl D, Itin P, Vahlquist A, Gobello T, Mazzanti C, Reggazini R, Nagy G, Munro CS, Strachan T: ATP2A2 mutations in Darier's disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. Hum Mol Genet. 1999 Sep;8(9):1621-30. doi: 10.1093/hmg/8.9.1621.
Pubmed: 10441324
Lytton J, MacLennan DH: Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene. J Biol Chem. 1988 Oct 15;263(29):15024-31.
Pubmed: 2844796
Komuro I, Wenninger KE, Philipson KD, Izumo S: Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4769-73. doi: 10.1073/pnas.89.10.4769.
Pubmed: 1374913
Van Eylen F, Bollen A, Herchuelz A: NCX1 Na/Ca exchanger splice variants in pancreatic islet cells. J Endocrinol. 2001 Mar;168(3):517-26. doi: 10.1677/joe.0.1680517.
Pubmed: 11241183
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Bagattin A, Veronese C, Rampazzo A, Danieli GA: Gene symbol: RYR2. Disease: Effort-induced polymorphic ventricular arrhythmias. Hum Genet. 2004 Mar;114(4):404.
Pubmed: 15046072
Tunwell RE, Wickenden C, Bertrand BM, Shevchenko VI, Walsh MB, Allen PD, Lai FA: The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis. Biochem J. 1996 Sep 1;318 ( Pt 2):477-87. doi: 10.1042/bj3180477.
Pubmed: 8809036
Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A: Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001 Feb 1;10(3):189-94. doi: 10.1093/hmg/10.3.189.
Pubmed: 11159936
Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, Liu X, Jiang Y, Bao X, Yao Z, Ding K, Lo WH, Qiang B, Chan P, Shen Y, Wu X: Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol. 2003 Aug;54(2):239-43. doi: 10.1002/ana.10607.
Pubmed: 12891677
Heron SE, Phillips HA, Mulley JC, Mazarib A, Neufeld MY, Berkovic SF, Scheffer IE: Genetic variation of CACNA1H in idiopathic generalized epilepsy. Ann Neurol. 2004 Apr;55(4):595-6. doi: 10.1002/ana.20028.
Pubmed: 15048902
Daniil G, Fernandes-Rosa FL, Chemin J, Blesneac I, Beltrand J, Polak M, Jeunemaitre X, Boulkroun S, Amar L, Strom TM, Lory P, Zennaro MC: CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism. EBioMedicine. 2016 Nov;13:225-236. doi: 10.1016/j.ebiom.2016.10.002. Epub 2016 Oct 4.
Pubmed: 27729216
Toyota M, Ho C, Ohe-Toyota M, Baylin SB, Issa JP: Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5' CpG island in human tumors. Cancer Res. 1999 Sep 15;59(18):4535-41.
Pubmed: 10493502
Morino H, Matsuda Y, Muguruma K, Miyamoto R, Ohsawa R, Ohtake T, Otobe R, Watanabe M, Maruyama H, Hashimoto K, Kawakami H: A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. Mol Brain. 2015 Dec 29;8:89. doi: 10.1186/s13041-015-0180-4.
Pubmed: 26715324
Chemin J, Siquier-Pernet K, Nicouleau M, Barcia G, Ahmad A, Medina-Cano D, Hanein S, Altin N, Hubert L, Bole-Feysot C, Fourage C, Nitschke P, Thevenon J, Rio M, Blanc P, Vidal C, Bahi-Buisson N, Desguerre I, Munnich A, Lyonnet S, Boddaert N, Fassi E, Shinawi M, Zimmerman H, Amiel J, Faivre L, Colleaux L, Lory P, Cantagrel V: De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. Brain. 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145.
Pubmed: 29878067
Soldatov NM: Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4628-32. doi: 10.1073/pnas.89.10.4628.
Pubmed: 1316612
Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, Sinke RJ, Weghuis DO, Klockner U, Wakamori M, et al.: Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6228-32. doi: 10.1073/pnas.90.13.6228.
Pubmed: 8392192
Soldatov NM: Genomic structure of human L-type Ca2+ channel. Genomics. 1994 Jul 1;22(1):77-87. doi: 10.1006/geno.1994.1347.
Pubmed: 7959794
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
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
Mische SM, Manjula BN, Fischetti VA: Relation of streptococcal M protein with human and rabbit tropomyosin: the complete amino acid sequence of human cardiac alpha tropomyosin, a highly conserved contractile protein. Biochem Biophys Res Commun. 1987 Feb 13;142(3):813-8. doi: 10.1016/0006-291x(87)91486-0.
Pubmed: 3548719
Lin CS, Leavitt J: Cloning and characterization of a cDNA encoding transformation-sensitive tropomyosin isoform 3 from tumorigenic human fibroblasts. Mol Cell Biol. 1988 Jan;8(1):160-8. doi: 10.1128/mcb.8.1.160.
Pubmed: 3336357
MacLeod AR, Gooding C: Human hTM alpha gene: expression in muscle and nonmuscle tissue. Mol Cell Biol. 1988 Jan;8(1):433-40. doi: 10.1128/mcb.8.1.433.
Pubmed: 3336363
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