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Pathway Description
Propranolol B2-Adrenergic Vasoconstriction Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-08-10
Last Updated: 2023-11-27
On the World Health Organization's List of Essential Medicines and a prototypical drug of its class, propranolol is a non-cardioselective beta blocker and it is typically synthesized as a racemic mixture of 2 enantiomers where the S(-)-enantiomer has approximately 100 times the binding affinity for beta adrenergic receptors. It can be administered intravenously to the bloodstream or orally, where it passes through hepatic portal circulation, and enters the bloodstream to act on peripheral cells. Propranolol is a non-selective beta adrenergic antagonist used to treat hypertension, angina, atrial fibrillation, myocardial infarction, migraine, essential tremor, hypertrophic subaortic stenosis, and pheochromocytoma. It can be found under the brand names Hemangeol, Hemangiol, Inderal, and Innopran. Propranolol causes vasoconstriction via blockage or antagonism of the beta-2 adrenergic receptors. By blocking these receptors, the G protein signalling cascade is unable to occur, leading to increased levels of intracellular calcium which can then readily bind to calmodulin causing smooth muscle contraction (vasoconstriction in this case). Some side effects of using propranolol may include dizziness, tiredness, and difficulties sleeping.
References
Propranolol B2-Adrenergic Vasoconstriction 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
Hagen R, Ghareeb E, Jalali O, Zinn Z: Infantile hemangiomas: what have we learned from propranolol? Curr Opin Pediatr. 2018 Aug;30(4):499-504. doi: 10.1097/MOP.0000000000000650.
Pubmed: 29846253
Khouri C, Jouve T, Blaise S, Carpentier P, Cracowski JL, Roustit M: Peripheral vasoconstriction induced by beta-adrenoceptor blockers: a systematic review and a network meta-analysis. Br J Clin Pharmacol. 2016 Aug;82(2):549-60. doi: 10.1111/bcp.12980. Epub 2016 May 31.
Pubmed: 27085011
Billington CK, Penn RB: Signaling and regulation of G protein-coupled receptors in airway smooth muscle. Respir Res. 2003;4(1):2. Epub 2003 Mar 14.
Pubmed: 12648290
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
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
Maldonado F, Hanks SK: A cDNA clone encoding human cAMP-dependent protein kinase catalytic subunit C alpha. Nucleic Acids Res. 1988 Aug 25;16(16):8189-90. doi: 10.1093/nar/16.16.8189.
Pubmed: 2843813
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
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
Beebe SJ, Oyen O, Sandberg M, Froysa A, Hansson V, Jahnsen T: Molecular cloning of a tissue-specific protein kinase (C gamma) from human testis--representing a third isoform for the catalytic subunit of cAMP-dependent protein kinase. Mol Endocrinol. 1990 Mar;4(3):465-75. doi: 10.1210/mend-4-3-465.
Pubmed: 2342480
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
Groussin L, Jullian E, Perlemoine K, Louvel A, Leheup B, Luton JP, Bertagna X, Bertherat J: Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease. J Clin Endocrinol Metab. 2002 Sep;87(9):4324-9. doi: 10.1210/jc.2002-020592.
Pubmed: 12213893
Sandberg M, Tasken K, Oyen O, Hansson V, Jahnsen T: Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis. Biochem Biophys Res Commun. 1987 Dec 31;149(3):939-45. doi: 10.1016/0006-291x(87)90499-2.
Pubmed: 3426618
Sandberg M, Skalhegg B, Jahnsen T: The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals. Biochem Biophys Res Commun. 1990 Feb 28;167(1):323-30. doi: 10.1016/0006-291x(90)91768-n.
Pubmed: 2310396
Manchev VT, Hilpert M, Berrou E, Elaib Z, Aouba A, Boukour S, Souquere S, Pierron G, Rameau P, Andrews R, Lanza F, Bobe R, Vainchenker W, Rosa JP, Bryckaert M, Debili N, Favier R, Raslova H: A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene. Blood. 2014 Oct 16;124(16):2554-63. doi: 10.1182/blood-2014-01-551820. Epub 2014 Jul 24.
Pubmed: 25061177
Reinton N, Haugen TB, Orstavik S, Skalhegg BS, Hansson V, Jahnsen T, Tasken K: The gene encoding the C gamma catalytic subunit of cAMP-dependent protein kinase is a transcribed retroposon. Genomics. 1998 Apr 15;49(2):290-7. doi: 10.1006/geno.1998.5240.
Pubmed: 9598317
Solberg R, Tasken K, Keiserud A, Jahnsen T: Molecular cloning, cDNA structure and tissue-specific expression of the human regulatory subunit RI beta of cAMP-dependent protein kinases. Biochem Biophys Res Commun. 1991 Apr 15;176(1):166-72. doi: 10.1016/0006-291x(91)90904-l.
Pubmed: 1708242
Solberg R, Tasken K, Wen W, Coghlan VM, Meinkoth JL, Scott JD, Jahnsen T, Taylor SS: Human regulatory subunit RI beta of cAMP-dependent protein kinases: expression, holoenzyme formation and microinjection into living cells. Exp Cell Res. 1994 Oct;214(2):595-605. doi: 10.1006/excr.1994.1297.
Pubmed: 7925653
Oyen O, Myklebust F, Scott JD, Hansson V, Jahnsen T: Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent protein kinase encodes an alternate amino-terminal region. FEBS Lett. 1989 Mar 27;246(1-2):57-64. doi: 10.1016/0014-5793(89)80253-4.
Pubmed: 2540040
Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. doi: 10.1038/nature04728.
Pubmed: 16641997
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