Adenosine signaling: a potential therapeutic target for psychogenic erectile dysfunction

Therapeutic modalities for psychogenic erectile dysfunction (PED) are poorly targeted because of the lack of specific pathological features. The common symptoms of PED include psychological stress-related negative emotions and erectile dysfunction. Exploring their common therapeutic targets is helpful in the development of effective PED treatment strategies. Adenosine locally acts as a vasodilator or neuromodulator in the penis and promotes erection. Recent studies have demonstrated that adenosine (ADO) signaling is also involved in psychological stress. Herein, we review the pathogenesis of PED and the interaction between ADO and the erection regulator nitric oxide (NO) in brain and penile tissues. In addition, we summarize the regulatory role of ADO signal transduction in penile erection, psychological stress and negative emotions. Through our study, we found that ADO is involved in psychological stress and erectile events by combining adenosine A₁ receptors (A₁R) and adenosine A_2A receptors (A_2AR). The application of A₁R selective agonists may promote erection and improve psychological state.