Introduction: Priapism is defined as abnormal prolonged penile erection lasting at least for 4 hours occurring without sexual interest. Forty percent of sickle cell disease (SCD) patients display priapism. The disorder is dangerous and urgent given its association with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. Current strategies to manage the disorder are poor due to lack of fundamental understanding of the molecular mechanisms of priapism. Adenosine is a signaling nucleoside that elicits many pathophysiological effects by engaging membrane receptors. Recent evidence shows that adenosine may play an important role in priapism via adenosine receptor.
Aim: To summarize the recent findings on the importance of adenosine signaling in the pathogenesis of priapism.
Main outcome measures: Evidence in the literature on the association between adenosine signaling and the development of priapism.
Methods: This article reviews the literature that relates to the contributory role of adenosine signaling in priapism in multiple animal models and humans.
Results: Excessive adenosine accumulation in the penis, coupled with increased A(2B)R signaling, contributes to priapism in two independent lines of mutant mice. One is adenosine deaminase (ADA)-deficient mice, the only animal displaying spontaneously prolonged penile erection, and the other is SCD transgenic mice, a well-accepted priapic animal model. Both polyethylene glycol-modified ADA (PEG-ADA) enzyme therapy and A(2B)R antagonists are capable of inhibiting potent corpus cavernosal vascular relaxation associated with priapic-like activity seen in both ADA-deficient mice and SCD transgenic mice, indicating that PEG-ADA enzyme therapy is likely to be a novel therapy for such a dangerous urological disorder.
Conclusion: Overall, the research reviewed here raises the intriguing possibility that elevated adenosine signaling contributes to priapism in general and that this signaling pathway represents a potentially important therapeutic target for the treatment of priapism.