Skip to main content
SpringerLink
Log in

Targeting Phosphodiesterases in Anti-platelet Therapy

  • Chapter
  • First Online:
Antiplatelet Agents

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 210))

Abstract

There are two primary modes of platelet inhibition: blockade of membrane receptors or neutralization of intracellular pathways. Both means of inhibition have proven benefits in the prevention and resolution of atherothrombotic events. With regard to intracellular inhibition, phosphodiesterases (PDEs) are fundamental for platelet function. Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. PDE inhibitors, such as cilostazol and dipyridamole, dampen platelet function by increasing cAMP and cGMP levels. This review focuses on the roles of PDE inhibitors in modulating platelet function, with particular attention paid to drugs that have anti-platelet clinical indications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adams RJ, Albers G, Alberts MJ et al (2008) Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 39:1647–1652

    Article  PubMed  Google Scholar 

  • Ahn HS, Crim W, Romano M et al (1989) Effects of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta. Biochem Pharmacol 38:3331–3339

    Article  PubMed  CAS  Google Scholar 

  • Akiyama H, Kudo S, Shimizu T et al (1985) The metabolism of a new antithrombotic and vasodilating agent, cilostazol, in rat, dog and man. Arzneimittelforschung 35:1133–1140

    PubMed  CAS  Google Scholar 

  • Aktas B, Utz A, Hoenig-Liedl P et al (2003) Dipyridamole enhances NO/cGMP-mediated vasodilator-stimulated phosphoprotein phosphorylation and signaling in human platelets: in vitro and in vivo/ex vivo studies. Stroke 34:764–769

    Article  PubMed  CAS  Google Scholar 

  • Aravind L, Ponting CP et al (1997) The GAF domain: an evolutionary link between diverse phototransducing proteins. Trends Biochem Sci 22:458–459

    Article  PubMed  CAS  Google Scholar 

  • Beavo JA et al (1995) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 75:725–748

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Berkels R, Klotz T, Sticht G et al (2001) Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil. J Cardiovasc Pharmacol 37:413–421

    Article  PubMed  CAS  Google Scholar 

  • Bramer SL, Forbes WP, Mallikaarjun S et al (1999) Cilostazol pharmacokinetics after single and multiple oral doses in healthy males and patients with intermittent claudication resulting from peripheral arterial disease. Clin Pharmacokinet 37(Suppl 2):1–11

    Article  PubMed  CAS  Google Scholar 

  • Brito FC, Kummerle AE, Lugnier C et al (2010) Novel thienylacylhydrazone derivatives inhibit platelet aggregation through cyclic nucleotides modulation and thromboxane A2 synthesis inhibition. Eur J Pharmacol 638:5–12

    Article  PubMed  CAS  Google Scholar 

  • Chakrabarti S, Freedman JE et al (2008) Dipyridamole, cerebrovascular disease, and the vasculature. Vascul Pharmacol 48:143–149

    Article  PubMed  CAS  Google Scholar 

  • Chesebro JH, Steele PM, Fuster V et al (1985) Platelet-inhibitor therapy in cardiovascular disease. Effective defense against thromboembolism. Postgrad Med 78(48–50):57–71

    Google Scholar 

  • Choi YH, Ekholm D, Krall J et al (2001) Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes. Biochem J 353:41–50

    Article  PubMed  CAS  Google Scholar 

  • Colman RW et al (2004) Platelet cyclic adenosine monophosphate phosphodiesterases: targets for regulating platelet-related thrombosis. Semin Thromb Hemost 30:451–460

    Article  PubMed  CAS  Google Scholar 

  • Colucci WS et al (1991) Cardiovascular effects of milrinone. Am Heart J 121:1945–1947

    Article  PubMed  CAS  Google Scholar 

  • Criqui MH, Fronek A, Barrett-Connor E et al (1985) The prevalence of peripheral arterial disease in a defined population. Circulation 71:510–515

    Article  PubMed  CAS  Google Scholar 

  • Dawson DL, Cutler BS, Hiatt WR et al (2000) A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 109:523–530

    Article  PubMed  CAS  Google Scholar 

  • De Bon E, Bonanni G, Saggiorato G et al (2010) Effects of tadalafil on platelets and endothelium in patients with erectile dysfunction and cardiovascular risk factors: a pilot study. Angiology 61:602–606

    Article  PubMed  Google Scholar 

  • Dickinson NT, Jang EK, Haslam RJ et al (1997) Activation of cGMP-stimulated phosphodiesterase by nitroprusside limits cAMP accumulation in human platelets: effects on platelet aggregation. Biochem J 323(Pt 2):371–377

    PubMed  CAS  Google Scholar 

  • Diebold I, Djordjevic T, Petry A et al (2009) Phosphodiesterase 2 mediates redox-sensitive endothelial cell proliferation and angiogenesis by thrombin via Rac1 and NADPH oxidase 2. Circ Res 104:1169–1177

    Article  PubMed  CAS  Google Scholar 

  • Diener HC, Cunha L, Forbes C et al (1996) European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 143:1–13

    Article  PubMed  CAS  Google Scholar 

  • Dobesh PP, Stacy ZA, Persson EL et al (2009) Pharmacologic therapy for intermittent claudication. Pharmacotherapy 29:526–553

    Article  PubMed  CAS  Google Scholar 

  • Dunkern TR, Hatzelmann A et al (2005) The effect of Sildenafil on human platelet secretory function is controlled by a complex interplay between phosphodiesterases 2, 3 and 5. Cell Signal 17:331–339

    Article  PubMed  CAS  Google Scholar 

  • Eisert WG (2007) Dipyridamole. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 1165–1179

    Chapter  Google Scholar 

  • Eldor A, Vlodavsky I, Fuks Z et al (1986) Different effects of aspirin, dipyridamole and UD-CG 115 on platelet activation in a model of vascular injury: studies with extracellular matrix covered with endothelial cells. Thromb Haemost 56:333–339

    PubMed  CAS  Google Scholar 

  • Faxon DP, Creager MA, Smith SC Jr et al (2004) Atherosclerotic Vascular Disease Conference: Executive summary: Atherosclerotic Vascular Disease Conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation 109:2595–2604

    Article  PubMed  Google Scholar 

  • Francis SH, Bessay EP, Kotera J et al (2002) Phosphorylation of isolated human phosphodiesterase-5 regulatory domain induces an apparent conformational change and increases cGMP binding affinity. J Biol Chem 277:47581–47587

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Franks ZG, Campbell RA, Weyrich AS et al (2010) Platelet-leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke. Ann N Y Acad Sci 1207:11–17

    Article  PubMed  CAS  Google Scholar 

  • Ge J, Han Y, Jiang H et al (2005) RACTS: a prospective randomized antiplatelet trial of cilostazol versus ticlopidine in patients undergoing coronary stenting: long-term clinical and angiographic outcome. J Cardiovasc Pharmacol 46:162–166

    Article  PubMed  CAS  Google Scholar 

  • Grant PG, Colman RW et al (1984) Purification and characterization of a human platelet cyclic nucleotide phosphodiesterase. Biochemistry 23:1801–1807

    Article  PubMed  CAS  Google Scholar 

  • Grant PG, Mannarino AF, Colman RW et al (1988) cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity. Proc Natl Acad Sci USA 85:9071–9075

    Article  PubMed  CAS  Google Scholar 

  • Grant PG, Mannarino AF, Colman RW et al (1990) Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from the cytosol of human platelets. Thromb Res 59:105–119

    Article  PubMed  CAS  Google Scholar 

  • Gresele P, Zoja C, Deckmyn H et al (1983) Dipyridamole inhibits platelet aggregation in whole blood. Thromb Haemost 50:852–856

    PubMed  CAS  Google Scholar 

  • Gresele P, Arnout J, Deckmyn H et al (1986) Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity. Thromb Haemost 55:12–18

    PubMed  CAS  Google Scholar 

  • Gresele P, Momi S, Falcinelli E et al (2011) Anti-platelet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 72(4):634–646

    Article  PubMed  CAS  Google Scholar 

  • Halcox JP, Nour KR, Zalos G et al (2002) The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia. J Am Coll Cardiol 40:1232–1240

    Article  PubMed  CAS  Google Scholar 

  • Halkes PH, van Gijn J, Kappelle LJ et al (2006) Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 367:1665–1673

    Article  PubMed  CAS  Google Scholar 

  • Han Y, Li Y, Wang S et al (2009) Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J 157:733–739

    Article  PubMed  CAS  Google Scholar 

  • Haslam RJ, Davidson MM, Davies T et al (1978) Regulation of blood platelet function by cyclic nucleotides. Adv Cyclic Nucleotide Res 9:533–552

    PubMed  CAS  Google Scholar 

  • Haslam RJ, Dickinson NT, Jang EK et al (1999) Cyclic nucleotides and phosphodiesterases in platelets. Thromb Haemost 82:412–423

    PubMed  CAS  Google Scholar 

  • Hiatt WR et al (2005) The US experience with cilostazol in treating intermittent claudication. Atheroscler Suppl 6:21–31

    Article  PubMed  CAS  Google Scholar 

  • Hidaka H, Asano T et al (1976) Human blood platelet 3′: 5′-cyclic nucleotide phosphodiesterase. Isolation of low-Km and high-Km phosphodiesterase. Biochim Biophys Acta 429:485–497

    Article  PubMed  CAS  Google Scholar 

  • Hunter RW, Mackintosh C, Hers I et al (2009) Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets. J Biol Chem 284:12339–12348

    Article  PubMed  CAS  Google Scholar 

  • Igawa T, Tani T, Chijiwa T et al (1990) Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. Thromb Res 57:617–623

    Article  PubMed  CAS  Google Scholar 

  • Ito M, Nishikawa M, Fujioka M et al (1996) Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021. Cell Signal 8:575–581

    Article  PubMed  CAS  Google Scholar 

  • Jennings DL, Kalus JS et al (2010) Addition of cilostazol to aspirin and a thienopyridine for prevention of restenosis after coronary artery stenting: a meta-analysis. J Clin Pharmacol 50:415–421

    Article  PubMed  CAS  Google Scholar 

  • Jung WK, Lee DY, Park C et al (2010) Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibiting mitogen-activated protein kinases. Br J Pharmacol 159:1274–1285

    Article  PubMed  CAS  Google Scholar 

  • Kariyazono H, Nakamura K, Shinkawa T et al (2001) Inhibition of platelet aggregation and the release of P-selectin from platelets by cilostazol. Thromb Res 101:445–453

    Article  PubMed  CAS  Google Scholar 

  • Kass DA, Champion HC, Beavo JA et al (2007) Phosphodiesterase type 5: expanding roles in cardiovascular regulation. Circ Res 101:1084–1095

    Article  PubMed  CAS  Google Scholar 

  • Kasuya J, Goko H, Fujita-Yamaguchi Y et al (1995) Multiple transcripts for the human cardiac form of the cGMP-inhibited cAMP phosphodiesterase. J Biol Chem 270:14305–14312

    Article  PubMed  CAS  Google Scholar 

  • Klabunde RE et al (1983) Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 93:21–26

    Article  PubMed  CAS  Google Scholar 

  • Lima LM, Ormelli CB, Brito FF et al (1999) Synthesis and antiplatelet evaluation of novel aryl-sulfonamide derivatives, from natural safrole. Pharm Acta Helv 73:281–292

    Article  PubMed  CAS  Google Scholar 

  • Lin CS, Lin G, Xin ZC et al (2006) Expression, distribution and regulation of phosphodiesterase 5. Curr Pharm Des 12:3439–3457

    Article  PubMed  CAS  Google Scholar 

  • Macphee CH, Reifsnyder DH, Moore TA et al (1988) Phosphorylation results in activation of a cAMP phosphodiesterase in human platelets. J Biol Chem 263:10353–10358

    PubMed  CAS  Google Scholar 

  • Masciarelli S, Horner K, Liu C et al (2004) Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility. J Clin Invest 114:196–205

    PubMed  CAS  Google Scholar 

  • Maurice DH, Haslam RJ et al (1990) Molecular basis of the synergistic inhibition of platelet function by nitrovasodilators and activators of adenylate cyclase: inhibition of cyclic AMP breakdown by cyclic GMP. Mol Pharmacol 37:671–681

    PubMed  CAS  Google Scholar 

  • Muggli R, Tschopp TB, Mittelholzer E et al (1985) 7-Bromo-1,5-dihydro-3,6-dimethylimidazo[2,1-b]quinazolin-2(3H)- one (Ro 15-2041), a potent antithrombotic agent that selectively inhibits platelet cyclic AMP-phosphodiesterase. J Pharmacol Exp Ther 235:212–219

    PubMed  CAS  Google Scholar 

  • Neri Serneri GG, Masotti G, Poggesi L et al (1981) Enhanced prostacyclin production by dipyridamole in man. Eur J Clin Pharmacol 21:9–15

    Article  PubMed  CAS  Google Scholar 

  • Nishio Y, Kashiwagi A, Takahara N et al (1997) Cilostazol, a cAMP phosphodiesterase inhibitor, attenuates the production of monocyte chemoattractant protein-1 in response to tumor necrosis factor-alpha in vascular endothelial cells. Horm Metab Res 29:491–495

    Article  PubMed  CAS  Google Scholar 

  • Okuda YKY, Yamashita K et al (1993) Cilostazol. Cardiovascu Drug Rev 11:451–465

    Article  CAS  Google Scholar 

  • Omori K, Kotera J et al (2007) Overview of PDEs and their regulation. Circ Res 100:309–327

    Article  PubMed  CAS  Google Scholar 

  • Palmer D, Maurice DH et al (2000) Dual expression and differential regulation of phosphodiesterase 3A and phosphodiesterase 3B in human vascular smooth muscle: implications for phosphodiesterase 3 inhibition in human cardiovascular tissues. Mol Pharmacol 58:247–252

    PubMed  CAS  Google Scholar 

  • Pratt CM et al (2001) Analysis of the cilostazol safety database. Am J Cardiol 87:28D–33D

    Article  PubMed  CAS  Google Scholar 

  • Rowley JW, Oler AJ, Tolley ND et al (2011) Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 118:e101–e111

    Article  PubMed  CAS  Google Scholar 

  • Russwurm C, Zoidl G, Koesling D et al (2009) Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes. J Biol Chem 284:25782–25790

    Article  PubMed  CAS  Google Scholar 

  • Sacco RL, Diener HC, Yusuf S et al (2008) Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 359:1238–1251

    Article  PubMed  CAS  Google Scholar 

  • Schror K et al (2002) The pharmacology of cilostazol. Diabetes Obes Metab 4(Suppl 2):S14–S19

    Article  PubMed  CAS  Google Scholar 

  • Seiler S, Arnold AJ, Grove RI et al (1987) Effects of anagrelide on platelet cAMP levels, cAMP-dependent protein kinase and thrombin-induced Ca++ fluxes. J Pharmacol Exp Ther 243:767–774

    PubMed  CAS  Google Scholar 

  • Shakur Y, Holst LS, Landstrom TR et al (2001) Regulation and function of the cyclic nucleotide phosphodiesterase (PDE3) gene family. Prog Nucleic Acid Res Mol Biol 66:241–277

    Article  PubMed  CAS  Google Scholar 

  • Shinohara Y, Katayama Y, Uchiyama S et al (2010) Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol 9:959–968

    Article  PubMed  CAS  Google Scholar 

  • Silverstein MN, Petitt RM, Solberg LA Jr et al (1988) Anagrelide: a new drug for treating thrombocytosis. N Engl J Med 318:1292–1294

    Article  PubMed  CAS  Google Scholar 

  • Stein PD, Alpert JS, Dalen JE et al (1998) Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 114:602S–610S

    Article  PubMed  CAS  Google Scholar 

  • Stephenson DT, Coskran TM, Wilhelms MB et al (2009) Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem 57:933–949

    Article  PubMed  CAS  Google Scholar 

  • Suh JW, Lee SP, Park KW et al (2011) Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol 57:280–289

    Article  PubMed  CAS  Google Scholar 

  • Sun B, Li H, Shakur Y et al (2007) Role of phosphodiesterase type 3A and 3B in regulating platelet and cardiac function using subtype-selective knockout mice. Cell Signal 19:1765–1771

    Article  PubMed  CAS  Google Scholar 

  • Tani T, Sakurai K, Kimura Y et al (1992) Pharmacological manipulation of tissue cyclic AMP by inhibitors. Effects of phosphodiesterase inhibitors on the functions of platelets and vascular endothelial cells. Adv Second Messenger Phosphoprotein Res 25:215–227

    PubMed  CAS  Google Scholar 

  • Theis JG, Deichsel G, Marshall S et al (1999) Rapid development of tolerance to dipyridamole-associated headaches. Br J Clin Pharmacol 48:750–755

    Article  PubMed  CAS  Google Scholar 

  • Thompson PD, Zimet R, Forbes WP et al (2002) Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. Am J Cardiol 90:1314–1319

    Article  PubMed  CAS  Google Scholar 

  • van Ryn J, Lorenz M, Merk H et al (2003) Accumulation of radiolabelled platelets and fibrin on the carotid artery of rabbits after angioplasty: effects of heparin and dipyridamole. Thromb Haemost 90:1179–1186

    PubMed  Google Scholar 

  • Venkatesh PK, Pattillo CB, Branch B et al (2010) Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite/nitric oxide-dependent pathway. Cardiovasc Res 85:661–670

    Article  PubMed  CAS  Google Scholar 

  • Verro P, Gorelick PB, Nguyen D et al (2008) Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: a meta-analysis. Stroke 39:1358–1363

    Article  PubMed  CAS  Google Scholar 

  • Wallis RM, Corbin JD, Francis SH et al (1999) Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 83:3C–12C

    Article  PubMed  CAS  Google Scholar 

  • Wang F, Li M, Cheng L et al (2008) Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats. Life Sci 83:828–835

    Article  PubMed  CAS  Google Scholar 

  • Wechsler J, Choi YH, Krall J et al (2002) Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes. J Biol Chem 277:38072–38078

    Article  PubMed  CAS  Google Scholar 

  • Weyrich AS, Denis MM, Kuhlmann-Eyre JR et al (2005) Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates. Circulation 111:633–642

    Article  PubMed  CAS  Google Scholar 

  • Weyrich AS, Kraiss LW, Prescott SM et al (2006) New roles for an old drug: inhibition of gene expression by dipyridamole in platelet-leukocyte aggregates. Trends Cardiovasc Med 16:75–80

    Article  PubMed  CAS  Google Scholar 

  • Yamagami H, Sakai N, Matsumaru Y et al (2012) Periprocedural cilostazol treatment and restenosis after carotid artery stenting: The Retrospective Study of In-Stent Restenosis after Carotid Artery Stenting (ReSISteR-CAS). J Stroke Cerebrovasc Dis 21(3):193–199

    Article  PubMed  Google Scholar 

  • Yang Q, Paskind M, Bolger G et al (1994) A novel cyclic GMP stimulated phosphodiesterase from rat brain. Biochem Biophys Res Commun 205:1850–1858

    Article  PubMed  CAS  Google Scholar 

  • Yoo HD, Cho HY, Lee YB et al (2010) Population pharmacokinetic analysis of cilostazol in healthy subjects with genetic polymorphisms of CYP3A5, CYP2C19 and ABCB1. Br J Clin Pharmacol 69:27–37

    Article  PubMed  CAS  Google Scholar 

  • Zoraghi R, Corbin JD, Francis SH et al (2004) Properties and functions of GAF domains in cyclic nucleotide phosphodiesterases and other proteins. Mol Pharmacol 65:267–278

    Article  PubMed  CAS  Google Scholar 

  • Zoraghi R, Bessay EP, Corbin JD et al (2005) Structural and functional features in human PDE5A1 regulatory domain that provide for allosteric cGMP binding, dimerization, and regulation. J Biol Chem 280:12051–12063

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Molecular Medicine Program and Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84112, USA

    Matthew T. Rondina & Andrew S. Weyrich Ph.D.

  2. Eccles Institute of Human Genetics, University of Utah, Building 533, Room 4220, 15 North 2030 East, Salt Lake City, UT, 84112, USA

    Andrew S. Weyrich Ph.D.

Authors
  1. Matthew T. Rondina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew S. Weyrich Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew S. Weyrich Ph.D. .

Editor information

Editors and Affiliations

  1. , Department of Internal Medicine, University of Perugia, Via E. dal Pozzo, Perugia, 06126, Italy

    Paolo Gresele

  2. Institute, The William Harvey Research, Charterhouse Square, London, EC1M6BQ, United Kingdom

    Gustav V. R Born

  3. Istituto di Farmacologia, Università Cattolica del S. Cuore, Largo F. Vito 1, Roma, 00168, Italy

    Carlo Patrono

  4. King's College London, Sackler Inst. Pulmonary Pharmacology, Waterloo Campus, London, SE1 9NH, United Kingdom

    Clive P. Page

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Rondina, M.T., Weyrich, A.S. (2012). Targeting Phosphodiesterases in Anti-platelet Therapy. In: Gresele, P., Born, G., Patrono, C., Page, C. (eds) Antiplatelet Agents. Handbook of Experimental Pharmacology, vol 210. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29423-5_9

Download citation

Publish with us

Policies and ethics

Search

Navigation