Adenosine Signaling, Priapism and Novel Therapies

Abstract

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. To summarize the recent findings on the importance of adenosine signaling in the pathogenesis of priapism. Evidence in the literature on the association between adenosine signaling and the development of priapism. This article reviews the literature that relates to the contributory role of adenosine signaling in priapism in multiple animal models and humans. 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. 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.