期刊
JOURNAL OF SEXUAL MEDICINE
卷 8, 期 8, 页码 2172-2180出版社
ELSEVIER SCI LTD
DOI: 10.1111/j.1743-6109.2011.02316.x
关键词
CD73; Erectile Function; Erectile Dysfunction; Penile Adenosine Production
资金
- NIDDK NIH HHS [R01 DK083559, R01 DK083559-04] Funding Source: Medline
Introduction. Adenosine has been implicated in normal and abnormal penile erection. However, a direct role of endogenous adenosine in erectile physiology and pathology has not been established. Aim. To determine the functional role of endogenous adenosine production in erectile function. Methods. CD73-deficient mice (CD73(-/-)) and age-matched wild-type (WT) mice were used. Some WT mice were treated with alpha, beta-methylene adenosine diphosphate (ADP) (APCP), a CD73-specific inhibitor. High-performance liquid chromatography was used to measure adenosine levels in mouse penile tissues. In vivo assessment of intracorporal pressure (ICP) normalized to mean arterial pressure (MAP) in response to electrical stimulation (ES) of the cavernous nerve was used. Main Outcome Measurement. The main outcome measures of this study were the in vivo assessment of initiation and maintenance of penile erection in WT mice and mice with deficiency in CD73 (ecto-5'-nucleotidase), a key cell-surface enzyme to produce extracellular adenosine. Results. Endogenous adenosine levels were elevated in the erected state induced by ES of cavernous nerve compared to the flaccid state in WT mice but not in CD73(-/-) mice. At cellular levels, we identified that CD73 was highly expressed in the neuronal, endothelial cells, and vascular smooth muscle cells in mouse penis. Functionally, we found that the ratio of ES-induced ICP to MAP in CD73(-/-) mice was reduced from 0.48 +/- 0.03 to 0.33 +/- 0.05 and ES-induced slope was reduced from 0.30 +/- 0.13 mm Hg/s to 0.15 +/- 0.05 mm Hg/s (both P < 0.05). The ratio of ES-induced ICP to MAP in APCP-treated WT mice was reduced from 0.49 +/- 0.03 to 0.38 +/- 0.06 and ES-induced slope was reduced from 0.29 +/- 0.11 mm Hg/s to 0.19 +/- 0.04 mm Hg/s (both P < 0.05). Conclusion. Overall, our findings demonstrate that CD73-dependent production of endogenous adenosine plays a direct role in initiation and maintenance of penile erection. Wen J, Dai Y, Zhang Y, Zhang W, Kellems RE, and Xia Y. Impaired erectile function in CD73-deficient mice with reduced endogenous penile adenosine production. J Sex Med 2011;8:2172-2180.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据