Tohoku J. Exp. Med., 2015 October, 237(2)

A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats

JIAMING WEN,¹ BOHAN WANG,¹ CHUANJUN DU,¹ GANG XU,¹ ZHEWEI ZHANG,¹ YI LI¹ and NAN ZHANG¹

¹Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED.

keywords —— A2B adenosine receptor; BAY 60-6583; diabetes; erectile dysfunction; intracavernosal pressure

© 2015 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2015, 237, 141-148

Correspondence: Bohan Wang, M.D., Ph.D., Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Jiefang Road 88, Hangzhou 310009, China.

e-mail: wang866@hotmail.com