title: New insights into the pathophysiology of sickle cell disease-associated priapism.
abstract: BACKGROUND
  Priapism is defined as an erectile disorder, in which erection persists uncontrollably without sexual purpose. The precise mechanisms involved in the development of sickle cell disease-associated priapism are ill defined.
  
  
  OBJECTIVE
  To summarize the recent developments that increase our understanding of the molecular mechanisms of priapism.
  
  
  METHODS
  This article reviews the literature (Medline search 2000-2010) that relates the key molecular signaling pathways that contribute to the development of priapism associated with sickle-cell disease. It focuses on basic science investigations using multiple animal models.
  
  
  METHODS
  The reader will be informed of the most current research regarding the role of endothelial nitric oxide synthase, phosphodiesterase type 5 (PDE5), adenosine, RhoA/Rho-kinase (ROCK), and opiorphins in the pathophysiology of priapism.
  
  
  RESULTS
  New concepts in the field of priapism research 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 in this regard is the notion of aberrant signaling of the endothelium-derived nitric oxide and PDE5 signal transduction pathway in the penis. Additionally, dysfunctional regulatory control of signal transduction systems which interact with this pathway such as adenosine and RhoA/Rho-kinase may contribute to the development of priapism. Recent investigations of opiorphins also demonstrate a role in regulating corporal smooth muscle tone and thereby dysregulation of erection physiology in priapism. These advances have paved the way for understanding this disorder as having a molecular pathogenesis.
  
  
  CONCLUSIONS
  As the science underlying priapism further emerges, increasingly effective therapeutics for sickle cell disease-associated priapism is certain to follow.
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, The James Buchanan Brady Urological Institute, Marburg, Baltimore, MD 21287, USA. tbivala1@jhmi.edu
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.forename: Biljana
authors.initials: B
authors.lastname: Musicki
authors.forename: Omer
authors.initials: O
authors.lastname: Kutlu
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
mesh_terms: D000241:Adenosine / Q000502:physiology; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D009842:Oligopeptides / Q000502:physiology; D010410:Penile Erection / Q000502:physiology; D011317:Priapism / Q000209:etiology* / Q000503:physiopathology; D012471:Salivary Proteins and Peptides / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D009842:Oligopeptides; D012471:Salivary Proteins and Peptides; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D020742:rhoA GTP-Binding Protein; D000241:Adenosine