Management of Erectile Function by Penile Purinergic P2 Receptors in the Diabetic Rat

Purpose: We determined the role of purine and pyrimidine nucleotides in erectile function in diabetic rats. Materials and Methods: A total of 60 adult male rats were divided into 2 groups, including 30 controls and 30 treated with streptozotocin (60 mg/kg) for 8 weeks to induce hyperglycemia. Changes in intracavernous pressure after intracrural injections of adenosine 5'triphosphate and adenosine 5'triphosphate analogues in control and diabetic rats, and the relaxant response to electrical field stimulation of precontracted corpus cavernosum smooth muscle in organ baths were investigated. The localization of P2X1, P2Y1 and P2Y2 receptors was assessed in penile tissue via an immunohistochemical approach. Results: Corpus cavernosum smooth muscle relaxation in vivo and by electrical field stimulation in vitro was significantly decreased in diabetic rats. Adenosine 5'triphosphate (P2X, P2Y), 2-methylthioadenosine 5'triphosphate (P2Y1) and uridine 5'-triphosphate (P2Y2) agonists but not alpha,beta-methylene adenosine 5'triphosphate (a P2X1 agonist) significantly improved the erectile response to electrical field stimulation in diabetic rat corpus cavernosum smooth muscle. Although intracavernous pressure/mean arterial pressure values in the rats were not restored in the presence of the P2X1 antagonist PPADS, the relaxation response to electrical field stimulation in isolated corpus cavernosum smooth muscle from diabetic rats was improved. Abundant immunoreactivity for PX1 and P2Y2 receptors was observed in penile tissues from diabetic rats compared to that from control rats. Conclusions: These results demonstrate 1) heterogeneous effects of purinergic agonists on corporeal function in diabetic rats, and 2) the activation of P2Y1 and P2Y2 receptor relaxation of corpus cavernosum smooth muscle to induce erection in rats and perhaps improve erectile function in men with diabetes.