Effect oflcariin on Cyclic GMP Levels and on the mRNA Expression of cGMP-binding cGMP-specific Phosphodiesterase （PDE5） in Penile Cavernosum

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 26; no. 4; pp. 460 - 462
• Main Author: 蒋兆健 胡本容 王嘉陵 汤强 谭艳 向继洲 刘菊妍
• Format: Journal Article
• Language: English
• Published: 2006
• Subjects: 基因表达; 病理机制; 磷酸二酯酶; 阴茎海绵体
• ISSN: 1672-0733; 1993-1352

Summary： To further investigate the mechanisms of action of icariin （ICA）, we assessed the effects of ICA on the in vitro formation of cGMP and cAMP in isolated rabbit corpus cavernosum. Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of ICA and the dose-dependent accumulation of cGMP and cAMP was determined in the tissues samples by means of ^125I radioimmunoassay. Responses of the isolated tissues preparations to ICA were compared with those obtained with the reference compounds sildenafil （Sild）. Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type Ⅴ （PDE5） in rat penis were also observed. After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction （RT-PCR）. The results showed that ICA increased cGMP concentrations directly （P〈0.05）, but there was no significant effect on cAMP concentrations （P〉0.05）. In the presence of sodium nitroprusside （SNP）, a stimulatory agent of cGMP, both ICA and Sild increased cGMP concentrations with increasing dose （P〈0.01）. Their EC50 was 4.62 （ICA） and 0.42 （Sild） μmol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly （P〉0.05）. There were PDE5A 1 and PDE5A2 mRNA expressions in rat cor- pus cavernosum with PDE5A2 being the dominant isoform. ICA could obviously inhibit these two isoforms mRNA expression in rat penis, and decrease PDE5A1 more pronouncedly （P〈 0.01）. The present study indicated that the aphrodisiac mechanisms of icariin involved the NO-cGMP signal transduction pathway, with increasing cGMP levels in the corpus cavernosum smooth muscle. The inhibitory effect of icariin on PDE5 mRNA expression, especially on PDE5A1, might account for its molecular mechanisms for its long-term activity.