Molecular and Cellular Biochemistry

, Volume 372, Issue 1–2, pp 211–220 | Cite as

Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC–PKC–CaMK II- and Janus kinase-dependent signaling pathway

  • Wagner Santos Coelho
  • Mauro Sola-Penna


Serotonin (5-HT) is a hormone that has been implicated in the regulation of many physiological and pathological events. One of the most intriguing properties of this hormone is its ability to up-regulate mitosis. Moreover, 5-HT stimulates glucose uptake and up-regulates PFK activity through the 5-HT2A receptor, resulting in the phosphorylation of a tyrosine residue of PFK and the intracellular redistribution of PFK within skeletal muscle. The present study investigated some of the signaling intermediates involved in the effects of 5-HT on 6-phosphofructo-1-kinase (PFK) regulation from skeletal muscle using kinetic assessments, immunoprecipitation, and western blotting assays. Our results demonstrate that 5-HT stimulates PFK from skeletal muscle via phospholipase C (PLC). The activation of PLC in skeletal muscle leads to the recruitment of protein kinase C (PKC) and calmodulin and the stimulation of calmodulin kinase II, which associates with PFK upon 5-HT action. Alternatively, 5-HT loses its ability to up-regulate PFK activity when Janus kinase is inhibited, suggesting that 5-HT is able to control glycolytic flux in the skeletal muscle of mice by recruiting different pathways and controlling PFK activity.


Glycolysis Phosphofructokinase Regulation Metabolism Hormone 



5-Hydroxytryptamine, serotonin


Calcium–calmodulin-dependent protein kinase type II


Filamentous actin




Glucose transporter


G-protein-coupled receptors






Phosphatidylinositol-3-phosphate kinase


Protein kinase C


Phospholipase C





This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Programa de Oncobiologia) and Programa de Núcleos de Excelência (PRONEX).


  1. 1.
    Leysen JE (2004) 5-HT2 receptors. Curr Drug Targets CNS Neurol Disord 3:11–26PubMedCrossRefGoogle Scholar
  2. 2.
    Harvey JA, Quinn JL, Liu R, Aloyo VJ, Romano AG (2004) Selective remodeling of rabbit frontal cortex: relationship between 5-HT2A receptor density and associative learning. Psychopharmacology 172:435–442. doi: 10.1007/s00213-003-1687-4 PubMedCrossRefGoogle Scholar
  3. 3.
    Aloyo VJ, Berg KA, Spampinato U, Clarke WP, Harvey JA (2009) Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors. Pharmacol Ther 121:160–173. doi: 10.1016/j.pharmthera.2008.10.010 PubMedCrossRefGoogle Scholar
  4. 4.
    Roth BL, Willins DL, Kristiansen K, Kroeze WK (1998) 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol Ther 79:231–257PubMedCrossRefGoogle Scholar
  5. 5.
    Cook EH Jr, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL (1994) Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor. J Neurochem 63:465–469PubMedCrossRefGoogle Scholar
  6. 6.
    Hajduch E, Rencurel F, Balendran A, Batty IH, Downes CP, Hundal HS (1999) Serotonin (5-hydroxytryptamine), a novel regulator of glucose transport in rat skeletal muscle. J Biol Chem 274:13563–13568PubMedCrossRefGoogle Scholar
  7. 7.
    Hajduch E, Dombrowski L, Darakhshan F, Rencurel F, Marette A, Hundal HS (1999) Biochemical localisation of the 5-HT2A (serotonin) receptor in rat skeletal muscle. Biochem Biophys Res Commun 257:369–372PubMedCrossRefGoogle Scholar
  8. 8.
    Assouline-Cohen M, Ben-Porat H, Beitner R (1998) Activation of membrane skeleton-bound phosphofructokinase in erythrocytes induced by serotonin. Mol Genet Metab 63:235–238PubMedCrossRefGoogle Scholar
  9. 9.
    Nebigil CG, Garnovskaya MN, Spurney RF, Raymond JR (1995) Identification of a rat glomerular mesangial cell mitogenic 5-HT2A receptor. Am J Physiol 268:F122–F127PubMedGoogle Scholar
  10. 10.
    Guillet-Deniau I, Burnol AF, Girard J (1997) Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway. J Biol Chem 272:14825–14829PubMedCrossRefGoogle Scholar
  11. 11.
    Banes AK, Shaw SM, Tawfik A, Patel BP, Ogbi S, Fulton D, Marrero MB (2005) Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin. Am J Physiol Cell Physiol 288:C805–C812. doi: 10.1152/ajpcell.00385.2004 PubMedCrossRefGoogle Scholar
  12. 12.
    Azmitia EC (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56:413–424PubMedCrossRefGoogle Scholar
  13. 13.
    Sola-Penna M, Da Silva D, Coelho WS, Marinho-Carvalho MM, Zancan P (2010) Regulation of mammalian muscle type 6-phosphofructo-1-kinase and its implication for the control of the metabolism. IUBMB Life 62:791–796. doi: 10.1002/iub.393 PubMedCrossRefGoogle Scholar
  14. 14.
    Coelho WS, Costa KC, Sola-Penna M (2007) Serotonin stimulates mouse skeletal muscle 6-phosphofructo-1-kinase through tyrosine-phosphorylation of the enzyme altering its intracellular localization. Mol Genet Metab 92:364–370PubMedCrossRefGoogle Scholar
  15. 15.
    Coelho WS, Da Silva D, Marinho-Carvalho MM, Sola-Penna M (2012) Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner. Int J Biochem Cell Biol 44:150–157. doi: 10.1016/j.biocel.2011.10.010 PubMedCrossRefGoogle Scholar
  16. 16.
    Luther MA, Lee JC (1986) The role of phosphorylation in the interaction of rabbit muscle phosphofructokinase with F-actin. J Biol Chem 261:1753–1759PubMedGoogle Scholar
  17. 17.
    Kuo HJ, Malencik DA, Liou RS, Anderson SR (1986) Factors affecting the activation of rabbit muscle phosphofructokinase by actin. Biochemistry 25:1278–1286PubMedCrossRefGoogle Scholar
  18. 18.
    Alves GG, Sola-Penna M (2003) Epinephrine modulates cellular distribution of muscle phosphofructokinase. Mol Genet Metab 78:302–306CrossRefGoogle Scholar
  19. 19.
    Silva AP, Alves GG, Araujo AH, Sola-Penna M (2004) Effects of insulin and actin on phosphofructokinase activity and cellular distribution in skeletal muscle. An Acad Bras Cienc 76:541–548PubMedCrossRefGoogle Scholar
  20. 20.
    Zancan P, Sola-Penna M (2005) Calcium influx: a possible role for insulin modulation of intracellular distribution and activity of 6-phosphofructo-1-kinase in human erythrocytes. Mol Genet Metab 86:392–400PubMedCrossRefGoogle Scholar
  21. 21.
    Zancan P, Sola-Penna M (2005) Regulation of human erythrocyte metabolism by insulin: cellular distribution of 6-phosphofructo-1-kinase and its implication for red blood cell function. Mol Genet Metab 86:401–411PubMedCrossRefGoogle Scholar
  22. 22.
    Real-Hohn A, Zancan P, Da Silva D, Martins ER, Salgado LT, Mermelstein CS, Gomes AM, Sola-Penna M (2010) Filamentous actin and its associated binding proteins are the stimulatory site for 6-phosphofructo-1-kinase association within the membrane of human erythrocytes. Biochimie 92:538–544. doi: 10.1016/j.biochi.2010.01.023 PubMedCrossRefGoogle Scholar
  23. 23.
    Maia JCC, Gomes SL, Juliani MH, Morel CM (1983) Preparation of [γ-32 P] and [α-32 P]-nucleoside triphosphate, with high specific activity. In: Morel CM (ed) Genes and antigenes of parasites: a laboratory manual. FIOCRUZ, Rio de Janeiro, pp 146–157Google Scholar
  24. 24.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  25. 25.
    Sola-Penna M, dos Santos AC, Alves GG, El-Bacha T, Faber-Barata J, Pereira MF, Serejo FC, Da Poian AT, Sorenson M (2002) A radioassay for phosphofructokinase-1 activity in cell extracts and purified enzyme. J Biochem Biophys Methods 50:129–140PubMedCrossRefGoogle Scholar
  26. 26.
    Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994) International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46:157–203PubMedGoogle Scholar
  27. 27.
    Conn PJ, Sanders-Bush E, Hoffman BJ, Hartig PR (1986) A unique serotonin receptor in choroid plexus is linked to phosphatidylinositol turnover. Proc Natl Acad Sci USA 83:4086–4088PubMedCrossRefGoogle Scholar
  28. 28.
    Lam DD, Heisler LK (2007) Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes. Expert Rev Mol Med 9:1–24. doi: 10.1017/S1462399407000245 PubMedCrossRefGoogle Scholar
  29. 29.
    Smrcka AV, Brown JH, Holz GG (2012) Role of phospholipase cepsilon in physiological phosphoinositide signaling networks. Cell Signal 24:1333–1343. doi: 10.1016/j.cellsig.2012.01.009 PubMedCrossRefGoogle Scholar
  30. 30.
    Ferris CD, Snyder SH (1992) IP3 receptors: ligand-activated calcium channels in multiple forms. Adv Second Messenger Phosphoprot Res 26:95–107Google Scholar
  31. 31.
    Marinho-Carvalho MM, Costa-Mattos PV, Spitz GA, Zancan P, Sola-Penna M (2009) Calmodulin upregulates skeletal muscle 6-phosphofructo-1-kinase reversing the inhibitory effects of allosteric modulators. Biochim et Biophys Acta 1794:1175–1180CrossRefGoogle Scholar
  32. 32.
    Marinho-Carvalho MM, Zancan P, Sola-Penna M (2006) Modulation of 6-phosphofructo-1-kinase oligomeric equilibrium by calmodulin: formation of active dimers. Mol Genet Metab 87:253–261PubMedCrossRefGoogle Scholar
  33. 33.
    Zancan P, Rosas AO, Marcondes MC, Marinho-Carvalho MM, Sola-Penna M (2007) Clotrimazole inhibits and modulates heterologous association of the key glycolytic enzyme 6-phosphofructo-1-kinase. Biochem Pharmacol 73:1520–1527PubMedCrossRefGoogle Scholar
  34. 34.
    Mahrenholz AM, Lan L, Mansour TE (1991) Phosphorylation of heart phosphofructokinase by Ca2+/calmodulin protein kinase. Biochem Biophys Res Commun 174:1255–1259. doi: 10.1016/0006-291X(91)91556-R PubMedCrossRefGoogle Scholar
  35. 35.
    Oufkir T, Arseneault M, Sanderson JT, Vaillancourt C (2010) The 5-HT 2A serotonin receptor enhances cell viability, affects cell cycle progression and activates MEK-ERK1/2 and JAK2-STAT3 signalling pathways in human choriocarcinoma cell lines. Placenta 31:439–447. doi: 10.1016/j.placenta.2010.02.019 PubMedCrossRefGoogle Scholar
  36. 36.
    Rane SG, Reddy EP (2000) Janus kinases: components of multiple signaling pathways. Oncogene 19:5662–5679. doi: 10.1038/sj.onc.1203925 PubMedCrossRefGoogle Scholar
  37. 37.
    Guillausseau PJ, Meas T, Virally M, Laloi-Michelin M, MÈdeau V, Kevorkian JP (2008) Abnormalities in insulin secretion in type 2 diabetes mellitus. Diabetes Metab 34:S43–S48PubMedCrossRefGoogle Scholar
  38. 38.
    Coelho RG, Calaça IdC, Celestrini DdM, Correia AH, Costa MASM, Sola-Penna M (2011) Clotrimazole disrupts glycolysis in human breast cancer without affecting non-tumoral tissues. Mol Genet Metab 103:394–398. doi: 10.1016/j.ymgme.2011.04.003 PubMedCrossRefGoogle Scholar
  39. 39.
    Da Silva D, Zancan P, Coelho WS, Gomez LS, Sola-Penna M (2010) Metformin reverses hexokinase and 6-phosphofructo-1-kinase inhibition in skeletal muscle, liver and adipose tissues from streptozotocin-induced diabetic mouse. Arch Biochem Biophys 496:53–60. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  40. 40.
    El-Bacha T, de Freitas MS, Sola-Penna M (2003) Cellular distribution of phosphofructokinase activity and implications to metabolic regulation in human breast cancer. Mol Genet Metab 79:294–299PubMedCrossRefGoogle Scholar
  41. 41.
    Grechi J, Marinho-Carvalho M, Zancan P, Cinelli LP, Gomes AMO, Rodrigues ML, Nimrichter L, Sola-Penna M (2011) Glucuronoxylomannan from Cryptococcus neoformans down-regulates the enzyme 6-phosphofructo-1-kinase of macrophages. J Biol Chem 286:14820–14829. doi: 10.1074/jbc.M110.177030 PubMedCrossRefGoogle Scholar
  42. 42.
    Leite TC, Coelho RG, Silva DD, Coelho WS, Marinho-Carvalho MM, Sola-Penna M (2011) Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice. FEBS Lett 585:92–98. doi: 10.1016/j.febslet.2010.11.009 PubMedCrossRefGoogle Scholar
  43. 43.
    Leite TC, Da Silva D, Coelho RG, Zancan P, Sola-Penna M (2007) Lactate favours the dissociation of skeletal muscle 6-phosphofructo-1-kinase tetramers down-regulating the enzyme and muscle glycolysis. Biochem J 408:123–130CrossRefGoogle Scholar
  44. 44.
    Meira DD, Marinho-Carvalho MM, Teixeira CA, Veiga VF, Da Poian AT, Holandino C, de Freitas MS, Sola-Penna M (2005) Clotrimazole decreases human breast cancer cells viability through alterations in cytoskeleton-associated glycolytic enzymes. Mol Genet Metab 84:354–362PubMedCrossRefGoogle Scholar
  45. 45.
    Spitz GA, Furtado CM, Sola-Penna M, Zancan P (2009) Acetylsalicylic acid and salicylic acid decrease tumor cell viability and glucose metabolism modulating 6-phosphofructo-1-kinase structure and activity. Biochem Pharmacol 77:46–53PubMedCrossRefGoogle Scholar
  46. 46.
    Michaelidis B, Rofalikou E, Beis I (1993) The effect of serotonin (5-hydroxytryptamine) on glycolysis in the perfused ventricle of the fresh-water bivalve Anodonta cygnea: evidence for phosphorylation dephosphorylation control of phosphofructokinase. J Exp Biol 180:15–25Google Scholar
  47. 47.
    Shum JK, Melendez JA, Jeffrey JJ (2002) Serotonin-induced MMP-13 production is mediated via phospholipase C, protein kinase C, and ERK1/2 in rat uterine smooth muscle cells. J Biol Chem 277:42830–42840. doi: 10.1074/jbc.M205094200 PubMedCrossRefGoogle Scholar
  48. 48.
    Oestreich EA, Malik S, Goonasekera SA, Blaxall BC, Kelley GG, Dirksen RT, Smrcka AV (2009) Epac and phospholipase cepsilon regulate Ca2+ release in the heart by activation of protein kinase cepsilon and calcium–calmodulin kinase II. J Biol Chem 284:1514–1522. doi: 10.1074/jbc.M806994200 PubMedCrossRefGoogle Scholar
  49. 49.
    Maier LS, Bers DM (2007) Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart. Cardiovasc Res 73:631–640. doi: 10.1016/j.cardiores.2006.11.005 PubMedCrossRefGoogle Scholar
  50. 50.
    Ase AR, Raouf R, Belanger D, Hamel E, Seguela P (2005) Potentiation of P2X1 ATP-gated currents by 5-hydroxytryptamine 2A receptors involves diacylglycerol-dependent kinases and intracellular calcium. J Pharmacol Exp Ther 315:144–154. doi: 10.1124/jpet.105.089045 PubMedCrossRefGoogle Scholar
  51. 51.
    Seager JM, Murphy TV, Garland CJ (1994) Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery. Br J Pharmacol 111:525–532PubMedCrossRefGoogle Scholar
  52. 52.
    Cohen ML, Wittenauer LA (1987) Serotonin receptor activation of phosphoinositide turnover in uterine, fundal, vascular, and tracheal smooth muscle. J Cardiovasc Pharmacol 10:176–181PubMedCrossRefGoogle Scholar
  53. 53.
    Nakaki T, Roth BL, Chuang DM, Costa E (1985) Phasic and tonic components in 5-HT2 receptor-mediated rat aorta contraction: participation of Ca++ channels and phospholipase C. J Pharmacol Exp Ther 234:442–446PubMedGoogle Scholar
  54. 54.
    Roth BL, Nakaki T, Chuang DM, Costa E (1986) 5-Hydroxytryptamine2 receptors coupled to phospholipase C in rat aorta: modulation of phosphoinositide turnover by phorbol ester. J Pharmacol Exp Ther 238:480–485PubMedGoogle Scholar
  55. 55.
    Chen-Zion M, Lilling G, Beitner R (1993) The dual effects of Ca2+ on binding of the glycolytic enzymes, phosphofructokinase and aldolase, to muscle cytoskeleton. Biochem Med Metab Biol 49:173–181PubMedCrossRefGoogle Scholar
  56. 56.
    Ashkenazy-Shahar M, Beitner R (1999) Effects of Ca2+-ionophore A23187 and calmodulin antagonists on regulatory mechanisms of glycolysis and cell viability of NIH-3T3 fibroblasts. Mol Genet Metab 67:334–342. doi: 10.1006/mgme.1999.2877 PubMedCrossRefGoogle Scholar
  57. 57.
    Assouline-Cohen M, Beitner R (1999) Effects of Ca2+ on erythrocyte membrane skeleton-bound phosphofructokinase, ATP levels, and hemolysis. Mol Genet Metab 66:56–61. doi: 10.1006/mgme.1998.2773 PubMedCrossRefGoogle Scholar
  58. 58.
    Orosz F, Christova TY, Ovadi J (1988) Functional in vitro test of calmodulin antagonism: effect of drugs on interaction between calmodulin and glycolytic enzymes. Mol Pharmacol 33:678–682PubMedGoogle Scholar
  59. 59.
    Orosz F, Kovacs J, Low P, Vertessy BG, Urbanyi Z, Acs T, Keve T, Ovadi J (1997) Interaction of a new bis-indol derivative, KAR-2 with tubulin and its antimitotic activity. Br J Pharmacol 121:947–954PubMedCrossRefGoogle Scholar
  60. 60.
    Beitner R (1998) Calmodulin antagonists and cell energy metabolism in health and disease. Mol Genet Metab 64:161–168PubMedCrossRefGoogle Scholar
  61. 61.
    Glass-Marmor L, Beitner R (1997) Detachment of glycolytic enzymes from cytoskeleton of melanoma cells induced by calmodulin antagonists. Eur J Pharmacol 328:241–248PubMedCrossRefGoogle Scholar
  62. 62.
    Lilling G, Beitner R (1990) Decrease in cytoskeleton-bound phosphofructokinase in muscle induced by high intracellular calcium, serotonin and phospholipase A2 in vivo. Int J Biochem 22:857–863PubMedCrossRefGoogle Scholar
  63. 63.
    Livnat T, Chen-Zion M, Beitner R (1993) Stimulatory effect of epidermal growth factor on binding of glycolytic enzymes to muscles cytoskeleton and the antagonistic action of calmodulin inhibitors. Biochem Med Metab Biol 50:24–34PubMedCrossRefGoogle Scholar
  64. 64.
    Penso J, Beitner R (2002) Detachment of glycolytic enzymes from cytoskeleton of Lewis lung carcinoma and colon adenocarcinoma cells induced by clotrimazole and its correlation to cell viability and morphology. Mol Genet Metab 76:181–188PubMedCrossRefGoogle Scholar
  65. 65.
    Penso J, Beitner R (2002) Clotrimazole decreases glycolysis and the viability of lung carcinoma and colon adenocarcinoma cells. Eur J Pharmacol 451:227–235PubMedCrossRefGoogle Scholar
  66. 66.
    Furtado CM, Marcondes MC, Sola-Penna M, de Souza ML, Zancan P (2012) Clotrimazole preferentially inhibits human breast cancer cell proliferation, viability and glycolysis. PLoS One 7:e30462. doi: 10.1371/journal.pone.0030462 PubMedCrossRefGoogle Scholar
  67. 67.
    Sola-Penna M (2008) Metabolic regulation by lactate. IUBMB Life 60:605–608PubMedCrossRefGoogle Scholar
  68. 68.
    Marcondes MC, Sola-Penna M, RdSG Torres, Zancan P (2011) Muscle-type 6-phosphofructo-1-kinase and aldolase associate conferring catalytic advantages for both enzymes. IUBMB Life 63:435–445. doi: 10.1002/iub.464 PubMedCrossRefGoogle Scholar
  69. 69.
    Marcondes MC, Sola-Penna M, Zancan P (2010) Clotrimazole potentiates the inhibitory effects of ATP on the key glycolytic enzyme 6-phosphofructo-1-kinase. Arch Biochem Biophys 497:62–67. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  70. 70.
    McKune CM, Watts SW (2001) Characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling. J Pharmacol Exp Ther 297:88–95PubMedGoogle Scholar
  71. 71.
    Ogden K, Thompson JM, Hickner Z, Huang T, Tang DD, Watts SW (2006) A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Am J Physiol Heart Circ Physiol 291:H2857–H2863. doi: 10.1152/ajpheart.00229.2006 PubMedCrossRefGoogle Scholar
  72. 72.
    Honda H, Oda H, Nakamoto T, Honda Z, Sakai R, Suzuki T, Saito T, Nakamura K, Nakao K, Ishikawa T, Katsuki M, Yazaki Y, Hirai H (1998) Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. Nat Genet 19:361–365. doi: 10.1038/1246 PubMedCrossRefGoogle Scholar
  73. 73.
    Tang DD, Tan J (2003) Role of Crk-associated substrate in the regulation of vascular smooth muscle contraction. Hypertension 42:858–863. doi: 10.1161/01.HYP.0000085333.76141.33 PubMedCrossRefGoogle Scholar
  74. 74.
    Tang DD, Tan J (2003) Downregulation of profilin with antisense oligodeoxynucleotides inhibits force development during stimulation of smooth muscle. Am J Physiol Heart Circ Physiol 285:H1528–H1536. doi: 10.1152/ajpheart.00188.2003 PubMedGoogle Scholar
  75. 75.
    Lu R, Alioua A, Kumar Y, Kundu P, Eghbali M, Weisstaub NV, Gingrich JA, Stefani E, Toro L (2008) c-Src tyrosine kinase, a critical component for 5-HT2A receptor-mediated contraction in rat aorta. J Physiol 586:3855–3869. doi: 10.1113/jphysiol.2008.153593 PubMedCrossRefGoogle Scholar
  76. 76.
    Quinn JC, Johnson-Farley NN, Yoon J, Cowen DS (2002) Activation of extracellular-regulated kinase by 5-hydroxytryptamine(2A) receptors in PC12 cells is protein kinase C-independent and requires calmodulin and tyrosine kinases. J Pharmacol Exp Ther 303:746–752. doi: 10.1124/jpet.102.038083 PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de FármacosFaculdade de Farmácia, Universidade Federal do Rio de JaneiroIlha do Fundão, Rio de JaneiroBrazil
  2. 2.Instituto de Bioquímica MédicaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

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