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Cyclic AMP Signaling

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Biology of Vascular Smooth Muscle: Vasoconstriction and Dilatation

Abstract

Adenosine 3′5′ cyclic monophosphate (cAMP) is the second messenger mediating vasodilatation induced by β2 adrenergic agonists, vasodilator prostaglandins, histamine, vasoactive intestinal peptide, etc. cAMP exerts its action primarily by the activation of cAMP-dependent kinase (PKA). The effects of cAMP may also be mediated by the exchange proteins directly activated by cAMP and the cyclic nucleotide-gated (CNG) channels. The cytosolic levels of cAMP reflect its synthesis by adenylyl cyclase and its hydrolysis by phosphodiesterases, particularly the type 4 phosphodiesterase. The major mechanisms underlying cAMP-mediated vasodilatation include the activation of potassium channels, the activation of myosin light chain phosphatase, and the inhibition of RhoA/Rho kinase signaling.

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References

  • Ahmad F, Degerman E, Manganiello VC (2012) Cyclic nucleotide phosphodiesterase 3 signaling complexes. Horm Metab Res 44:776–785

    Article  CAS  PubMed  Google Scholar 

  • Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488–520

    Article  CAS  PubMed  Google Scholar 

  • Biel M (2009 Apr 3) Cyclic nucleotide-regulated cation channels. J Biol Chem 284(14):9017–9021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bobin P, Belacel-Ouari M, Bedioune I, Zhang L, Leroy J, Leblais V, Fischmeister R, Vandecasteele G (2016) Cyclic nucleotide phosphodiesterases in heart and vessels: a therapeutic perspective. Arch Cardiovasc Dis 109:431–443

    Article  PubMed  Google Scholar 

  • Boras BW, Kornev A, Taylor SS, McCulloch AD (2014) Using Markov state models to develop a mechanistic understanding of protein kinase A regulatory subunit RIα activation in response to cAMP binding. J Biol Chem 289:30040–30051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng KT, Leung YK, Shen B, Kwok YC, Wong CO, Kwan HY, Man YB, Ma X, Huang Y, Yao X (2008) CNGA2 channels mediate adenosine adenosine-induced Ca 2+ influx in vascular endothelial cells. Arterioscler Thromb Vasc Biol 28:913–918

    Article  CAS  PubMed  Google Scholar 

  • Ford CA, Mahajan P, Tabrizchi R (2011) Characterization of β-adrenoceptor-mediated relaxation signals in isolated pulmonary artery of Dahl salt-sensitive hypertensive and normotensive rats. Auton Autacoid Pharmacol 31:1–12

    Article  CAS  PubMed  Google Scholar 

  • Foster MN, Coetzee WA (2016) KATP channels in the cardiovascular system. Physiol Rev 96:177–252

    Article  CAS  PubMed  Google Scholar 

  • Francis SH, Blount MA, Corbin JD (2011) Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev 91:651–690

    Article  CAS  PubMed  Google Scholar 

  • Gao Y, Tolsa J-F, Shen H, Raj JU (1998) Effect of selective phosphodiesterase inhibitors on the responses of ovine pulmonary veins to prostaglandin E2. J Appl Physiol 84:13–18

    CAS  PubMed  Google Scholar 

  • Gofman Y, Schärfe C, Marks DS, Haliloglu T, Ben-Tal N (2014) Structure, dynamics and implied gating mechanism of a human cyclic nucleotide-gated channel. PLoS Comput Biol 10:e1003976

    Article  PubMed  PubMed Central  Google Scholar 

  • Grassie ME, Sutherland C, Ulke-Lemée A, Chappellaz M, Kiss E, Walsh MP, MacDonald JA (2012) Cross-talk between Rho-associated kinase and cyclic nucleotide-dependent kinase signaling pathways in the regulation of smooth muscle myosin light chain phosphatase. J Biol Chem 287:36356–36369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halls ML, Cooper DM (2011) Regulation by Ca2+-signaling pathways of adenylyl cyclases. Cold Spring Harb Perspect Biol 3:a004143

    Article  PubMed  PubMed Central  Google Scholar 

  • Hurley JH (1999) Structure, mechanism, and regulation of mammalian adenylyl cyclase. J Biol Chem 274:7599–7602

    Article  CAS  PubMed  Google Scholar 

  • Jourdan KB, Mason NA, Long L, Philips PG, Wilkins MR, Morrell NW (2001) Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 280:L1359–L1369

    CAS  PubMed  Google Scholar 

  • Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82:769–824

    Article  CAS  PubMed  Google Scholar 

  • Keravis T, Lugnier C (2012) Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br J Pharmacol 165:1288–1305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwan HY, Cheng KT, Ma Y, Huang Y, Tang NL, Yu S, Yao X (2010) CNGA2 contributes to ATP-induced noncapacitative Ca2+ influx in vascular endothelial cells. J Vasc Res 47:148–156

    Article  CAS  PubMed  Google Scholar 

  • Lefkimmiatis K, Zaccolo M (2014) cAMP signaling in subcellular compartments. Pharmacol Ther 143:295–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lezoualc'h F, Fazal L, Laudette M, Conte C (2016) Cyclic AMP sensor EPAC proteins and their role in cardiovascular function and disease. Circ Res 118:881–897

    Article  PubMed  Google Scholar 

  • Linder JU (2006) Class III adenylyl cyclases: molecular mechanisms of catalysis and regulation. Cell Mol Life Sci 63:1736–1751

    Article  CAS  PubMed  Google Scholar 

  • Loirand G, Guilluy C, Pacaud P (2006) Regulation of rho proteins by phosphorylation in the cardiovascular system. Trends Cardiovasc Med 16:199–204

    Article  CAS  PubMed  Google Scholar 

  • Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC (2014) Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov 13:290–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mundiña-Weilenmann C, Vittone L, Rinaldi G, Said M, de Cingolani GC, Mattiazzi A (2000) Endoplasmic reticulum contribution to the relaxant effect of cGMP- and cAMP-elevating agents in feline aorta. Am J Physiol Heart Circ Physiol 278:H1856–H1865

    PubMed  Google Scholar 

  • Nelson CP, Rainbow RD, Brignell JL, Perry MD, Willets JM, Davies NW, Standen NB, Challiss RA (2011) Principal role of adenylyl cyclase 6 in K+ channel regulation and vasodilator signalling in vascular smooth muscle cells. Cardiovasc Res 91:694–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olschewski A, Li Y, Tang B, Hanze J, Eul B, Bohle RM, Wilhelm J, Morty RE, Brau ME, Weir EK, Kwapiszewska G, Klepetko W, Seeger W, Olschewski H (2006) Impact of TASK-1 in human pulmonary artery smooth muscle cells. Circ Res 98:1072–1080

    Article  CAS  PubMed  Google Scholar 

  • Roberts OL, Dart C (2014) cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP). Biochem Soc Trans 42:89–97

    Article  CAS  PubMed  Google Scholar 

  • Roberts OL, Kamishima T, Barrett-Jolley R, Quayle JM, Dart C (2013) Exchange protein activated by cAMP (Epac) induces vascular relaxation by activating Ca2+-sensitive K+ channels in rat mesenteric artery. J Physiol 591:5107–5123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross GR, Yallampalli C (2006) Endothelium-independent relaxation by adrenomedullin in pregnant rat mesenteric artery: role of cAMP-dependent protein kinase A and calcium-activated potassium channels. J Pharmacol Exp Ther 317:1269–1275

    Article  CAS  PubMed  Google Scholar 

  • Sassone-Corsi P (2012) The cyclic AMP pathway. Cold Spring Harb Perspect Biol 4. pii:a011148

    Google Scholar 

  • Schmid A, Meili D, Salathe M (2014) Soluble adenylyl cyclase in health and disease. Biochim Biophys Acta 1842:2584–2592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt M, Dekker FJ, Maarsingh H (2013) Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol Rev 65:670–709

    Article  PubMed  Google Scholar 

  • Shen B, Cheng KT, Leung YK, Kwok YC, Kwan HY, Wong CO, Chen ZY, Huang Y, Yao X (2008) Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels. J Mol Cell Cardiol 45:437–445

    Article  CAS  PubMed  Google Scholar 

  • Skalhegg BS, Tasken K (2000) Specificity in the cAMP/PKA signaling pathway. Differential expression, regulation, and subcellular localization of subunits of PKA. Front Biosci 5:D678–D693

    CAS  PubMed  Google Scholar 

  • Steegborn C (2014) Structure, mechanism, and regulation of soluble adenylyl cyclases - similarities and differences to transmembrane adenylyl cyclases. Biochim Biophys Acta 1842:2535–2547

    Article  CAS  PubMed  Google Scholar 

  • Sutherland EW, Rall TW (1958) Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem 232:1077–1091

    CAS  PubMed  Google Scholar 

  • Taylor SS, Ilouz R, Zhang P, Kornev AP (2012) Assembly of allosteric macromolecular switches: lessons from PKA. Nat Rev Mol Cell Biol 13:646–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valsecchi F, Ramos-Espiritu LS, Buck J, Levin LR, Manfredi G (2013) cAMP and mitochondria. Physiology (Bethesda) 28:199–209

    Article  CAS  Google Scholar 

  • Wong CO, Yao X (2008) Cyclic nucleotide-gated channels: a familiar channel family with a new function? Futur Cardiol 4:505–515

    Article  CAS  Google Scholar 

  • Wooldridge AA, MacDonald JA, Erdodi F, Ma C, Borman MA, Hartshorne DJ, Haystead TA (2004) Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J Biol Chem 279:34496–34504

    Article  CAS  PubMed  Google Scholar 

  • Xin W, Feinstein WP, Britain AL, Ochoa CD, Zhu B, Richter W, Leavesley SJ, Rich TC (2015) Estimating the magnitude of near-membrane PDE4 activity in living cells. Am J Physiol Cell Physiol 309:C415–C424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Shi Y, Guo S, Zhang S, Cui N, Shi W, Zhu D, Jiang C (2008) PKA-dependent activation of the vascular smooth muscle isoform of KATP channels by vasoactive intestinal polypeptide and its effect on relaxation of the mesenteric resistance artery. Biochim Biophys Acta 1778:88–96

    Article  CAS  PubMed  Google Scholar 

  • Zhai K, Hubert F, Nicolas V, Ji G, Fischmeister R, Leblais V (2012) β-Adrenergic cAMP signals are predominantly regulated by phosphodiesterase type 4 in cultured adult rat aortic smooth muscle cells. PLoS One 7:e47826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zieba BJ, Artamonov MV, Jin L, Momotani K, Ho R, Franke AS, Neppl RL, Stevenson AS, Khromov AS, Chrzanowska-Wodnicka M, Somlyo AV (2011) The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity. J Biol Chem 286:16681–16692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China

    Yuansheng Gao

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Gao, Y. (2017). Cyclic AMP Signaling. In: Biology of Vascular Smooth Muscle: Vasoconstriction and Dilatation. Springer, Singapore. https://doi.org/10.1007/978-981-10-4810-4_13

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