Skip to main content
SpringerLink
Log in

Molecular science of priapism

  • Erectile Dysfunction
  • Published:
Current Sexual Health Reports Aims and scope Submit manuscript

Abstract

Priapism refers to the nonwillful persistence of penile erection in the absence of sexual excitation, and thus it constitutes a true sexual dysfunction. At present, the precise pathophysiologic basis for the disorder remains largely misunderstood, particularly with respect to its recurrent or “stuttering” clinical presentations. New concepts in this field of study suggest that priapism often results from altered vascular homeostatic actions in the penis and is associated with deficient erection control mechanisms on a molecular level. A leading proposal is that aberrant signaling of the nitric oxide signal transduction pathway in the penis is a principal mechanism. Additionally, dysfunctional regulatory control of signal transduction systems that interact with this pathway may contribute to the display of priapism. These advances have paved the way for understanding this disorder as having a molecular pathogenesis. As the molecular science underlying priapism further emerges, increasingly effective therapeutics for priapism are certain to follow.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Emond AM, Holman R, Hayes RJ, et al.:Priapism and impotence in homozygous sickle cell disease.Arch Intern Med 1980,140:1434–1437.

    Article  PubMed  CAS  Google Scholar 

  2. Fowler JE Jr, Koshy M, Strub M, Chinn SK:Priapism associated with the sickle cell hemoglobinopathies: prevalence, natural history and sequelae.J Urol 1991,145:65–68.

    PubMed  Google Scholar 

  3. Adeyoju AB, Olujohungbe AB, Morris J, et al.:Priapism in sickle-cell disease; incidence, risk factors and complications-an international multicentre study.BJU Int 2002,90:898–902.

    Article  PubMed  CAS  Google Scholar 

  4. Hinman F:Priapism. Report of cases and a clinical study of the literature with reference to its pathogenesis and surgical treatment.Ann Surg 1914,60:689–716.

    Article  PubMed  CAS  Google Scholar 

  5. Serjeant GR, de Ceulaer K, Maude GH:Stilboestrol and stuttering priapism in homozygous sickle-cell disease.Lancet 1985,2:1274–1276.

    Article  PubMed  CAS  Google Scholar 

  6. Burnett AL:Pathophysiology of priapism: dysregulatory erection physiology thesis.J Urol 2003,170:26–34.

    Article  PubMed  Google Scholar 

  7. Van der Horst C, Stuebinger H, Seif C, et al.:Priapism-etiology, pathophysiology and management.Int Braz J Urol 2003,29:391–400.

    PubMed  Google Scholar 

  8. Montague DK, Jarow J, Broderick GA, et al.:American Urological Association guideline on the management of priapism.J Urol 2003,170:1318–1324.

    Article  PubMed  Google Scholar 

  9. Berger R, Billups K, Brock G, et al.:Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.Int J Impot Res 2001,13(Suppl 5):S39-S43.

    PubMed  Google Scholar 

  10. Pryor J, Akkus E, Alter G, et al.:Priapism.J Sex Med 2004,1:116–120.

    Article  PubMed  Google Scholar 

  11. Burnett AL, Musicki B:The nitric oxide signaling pathway in the penis.Curr Pharm Des 2005,11:3987–3994.

    Article  PubMed  CAS  Google Scholar 

  12. Bivalacqua TJ, Usta MF, Champion HC, et al.:Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease.J Androl 2003,24(6 Suppl):S17-S37.

    PubMed  CAS  Google Scholar 

  13. Burnett AL:Novel nitric oxide signaling mechanisms regulate the erectile response.Int J Impot Res 2004,16(Suppl 1):S15-S19.

    Article  PubMed  CAS  Google Scholar 

  14. Ignarro LJ, Bush PA, Buga GM, et al.:Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle.Biochem Biophys Res Commun 1990,170:843–850.

    Article  PubMed  CAS  Google Scholar 

  15. Trigo-Rocha F, Hsu GL, Donatucci CF, Lue TF:The role of cyclic adenosine monophosphate, cyclic guanosine monophosphate, endothelium and nonadrenergic, noncholinergic neurotransmission in canine penile erection.J Urol 1993,149:872–877.

    PubMed  CAS  Google Scholar 

  16. Ammendola A, Geiselhoringer A, Hofmann F, Schlossmann J:Molecular determinants of the interaction between the inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase Ibeta.J Biol Chem 2001,276:24153–24159.

    Article  PubMed  CAS  Google Scholar 

  17. Christ GJ, Wang HZ, Venkateswarlu K, et al.:Ion Channels and Gap Junctions: Their Role in Erectile Physiology, Dysfunction, and Future Therapy.Mol Urol 1999,3:61–73.

    PubMed  CAS  Google Scholar 

  18. Chitaley K, Wingard CJ, Clinton Webb R, et al.:Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway.Nat Med 2001,7:119–122.

    Article  PubMed  CAS  Google Scholar 

  19. Takahashi R, Nishimura J, Hirano K, et al.:Modulation of Ca2+ sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle.J Urol 2003,169:2412–2416.

    Article  PubMed  CAS  Google Scholar 

  20. Bivalacqua TJ, Champion HC, Usta MF, et al.:RhoA/Rhokinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction.Proc Natl Acad Sci U S A 2004,101:9121–9126.

    Article  PubMed  CAS  Google Scholar 

  21. Jin L, Burnett AL:RhoA/Rho-kinase in erectile tissue: mechanisms of disease and therapeutic insights.Clin Sci (Lond) 2006,110:153–165.

    Article  CAS  Google Scholar 

  22. Somlyo AP, Somlyo AV:Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase.Physiol Rev 2003,83:1325–1358.

    PubMed  CAS  Google Scholar 

  23. Burnett AL:Phosphodiesterase 5 mechanisms and therapeutic applications.Am J Cardiol 2005,96:29M-31M.

    Article  PubMed  CAS  Google Scholar 

  24. Hurt KJ, Musicki B, Palese MA, et al.:Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection.Proc Natl Acad Sci U S A 2002,99:4061–4066.

    Article  PubMed  CAS  Google Scholar 

  25. Musicki B, Palese MA, Crone JK, Burnett AL:Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection.Biol Reprod 2004,70:282–289.

    Article  PubMed  CAS  Google Scholar 

  26. Of major importance Champion HC, Bivalacqua TJ, Takimoto E, et al.:Phosphodiesterase-5A on dysregulation in penile erectile tissue is a mechanism of priapism.Proc Natl Acad Sci USA 2005,102:1661–1666. This study offered a first-time scientifically based concept for the molecular mechanism of priapism.

    Article  PubMed  CAS  Google Scholar 

  27. Bivalacqua TJ, Liu T, Musicki B, et al.:Endothelial Nitric Oxide Synthase Keeps Erection Regulatory Function Balance in the Penis.Eur Urol 2006. Epub ahead of print.

  28. Gopal VK, Francis SH, Corbin JD:Allosteric sites of phosphodiesterase-5 (PDE5). A potential role in negative feedback regulation of cGMP signaling in corpus cavernosum.Eur J Biochem 2001,268:3304–3312.

    Article  PubMed  CAS  Google Scholar 

  29. Lin CS, Chow S, Lau A, et al.:Human PDE5A gene encodes three PDE5 isoforms from two alternate promoters.Int J Impot Res 2002,14:15–24.

    Article  PubMed  Google Scholar 

  30. Lin G, Xin ZC, Lue TF, Lin CS:Up and down-regulation of phosphodiesterase-5 as related to tachyphylaxis and priapism.J Urol 2003,170:S15-S18; discussion S19.

    Article  PubMed  Google Scholar 

  31. Musicki B, Champion HC, Becker RE, et al.:In vivo analysis of chronic phosphodiesterase-5 inhibition with sildenafil in penile erectile tissues: no tachyphylaxis effect.J Urol 2005,174:1493–1496.

    Article  PubMed  CAS  Google Scholar 

  32. Hinman F Jr:Priapism; reasons for failure of therapy.J Urol 1960,83:420–428.

    PubMed  Google Scholar 

  33. Burt FB, Schirmer HK, Scott WW:A new concept in the management of priapism.J Urol 1960,83:60–61.

    PubMed  CAS  Google Scholar 

  34. Hauri D, Spycher M, Bruhlmann W:Erection and priapism: a new physiopathological concept.Urol Int 1983,38:138–145.

    PubMed  CAS  Google Scholar 

  35. Lue TF, Hellstrom WJ, McAninch JW, Tanagho EA:Priapism: a refined approach to diagnosis and treatment.J Urol 1986,136:104–108.

    PubMed  CAS  Google Scholar 

  36. Levine JF, Saenz de Tejada I, Payton TR, Goldstein I:Recurrent prolonged erections and priapism as a sequela of priapism: pathophysiology and management.J Urol 1991,145:764–767.

    PubMed  CAS  Google Scholar 

  37. Melman A, Serels S:Priapism.Int J Impot Res 2000,12(Suppl 4):S133-S139.

    Article  PubMed  Google Scholar 

  38. Spycher MA, Hauri D:The ultrastructure of the erectile tissue in priapism.J Urol 1986,135:142–147.

    PubMed  CAS  Google Scholar 

  39. Broderick GA, Gordon D, Hypolite J, Levin RM:Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism.J Urol 1994,151:259–262.

    PubMed  CAS  Google Scholar 

  40. Saenz de Tejada I, Kim NN, Daley JT, et al.:Acidosis impairs rabbit trabecular smooth muscle contractility.J Urol 1997,157:722–726.

    Article  PubMed  CAS  Google Scholar 

  41. Muneer A, Cellek S, Dogan A, et al.:Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model.Int J Impot Res 2005,17:10–18.

    Article  PubMed  CAS  Google Scholar 

  42. Evliyaoglu Y, Kayrin L, Kaya B:Effect of allopurinol on lipid peroxidation induced in corporeal tissue by veno-occlusive priapism in a rat model.Br J Urol 1997,80:476–479.

    PubMed  CAS  Google Scholar 

  43. Munarriz R, Park K, Huang YH, et al.:Reperfusion of ischemic corporal tissue: physiologic and biochemical changes in an animal model of ischemic priapism.Urology 2003,62:760–764.

    Article  PubMed  Google Scholar 

  44. Ul-Hasan M, El-Sakka AI, Lee C, et al.:Expression of TGF-beta-1 mRNA and ultrastructural alterations in pharmacologically induced prolonged penile erection in a canine model.J Urol 1998,160:2263–2266.

    Article  PubMed  CAS  Google Scholar 

  45. Beuzard Y:Transgenic mouse models of sickle cell disease.Curr Opin Hematol 1996,3:150–155.

    Article  PubMed  CAS  Google Scholar 

  46. Adams DD, Lucas WO, Williams BG, et al.:A mouse genetic locus with death clock and life clock features.Mech Ageing Dev 2001,122:173–189.

    Article  PubMed  CAS  Google Scholar 

  47. Burnett AL, Chang AG, Crone JK, et al.:Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase.J Androl 2002,23:92–97.

    PubMed  CAS  Google Scholar 

  48. Musicki B, Champion HC, Becker RE, et al.:Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation.Mol Pharmacol 2005,68:226–232.

    PubMed  CAS  Google Scholar 

  49. Bivalacqua TJ, Champion HC, Mason W, et al.:Long-term phosphodiesterase type 5 inhibitor therapy reduces priapic activity in transgenic sickle cell mice [abstract].J Urol 2006,175:387.

    Google Scholar 

  50. Of major importance Burnett AL, Bivalacqua TJ, Champion HC, et al.:Longterm oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism.Urology 2006,67:1043–1048. This report presented the rationale and early success of using PDE5 inhibitors for the treatment of recurrent priapism.

    Article  PubMed  Google Scholar 

  51. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B:Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism.J Sex Med 2006,3:1077–1084.

    Article  PubMed  CAS  Google Scholar 

  52. Sanli O, Armagan A, Kandirali E, et al.:TGF-beta1 neutralizing antibodies decrease the fibrotic effects of ischemic priapism.Int J Impot Res 2004,16:492–497.

    Article  PubMed  CAS  Google Scholar 

  53. Rajfer J, Gore JL, Kaufman J, et al.:Case report: Avoidance of palpable corporal fibrosis due to priapism with upregulators of nitric oxide.J Sex Med 2006,3:173–176.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, The John’s Hopkins Hospital, 600 North Wolfe Street, Marburg 407, 21287-2411, Baltimore, MD, USA

    Arthur L. Burnett MD

Authors
  1. Arthur L. Burnett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Biljana Musicki PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Trinity J. Bivalacqua MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arthur L. Burnett MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burnett, A.L., Musicki, B. & Bivalacqua, T.J. Molecular science of priapism. Curr Sex Health Rep 4, 9–14 (2007). https://doi.org/10.1007/BF02938325

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02938325

Keywords

Search

Navigation