Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penile cavernosum

  • Jiang Zhaojian  (蒋兆健)
  • Hu Benrong  (胡本容)
  • Wang Jialing  (王嘉陵)
  • Tang Qiang  (汤强)
  • Tan Yan  (谭艳)
  • Xiang Jizhou  (向继洲)
  • Liu Juyan  (刘菊妍)
Article

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) μ mol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly (P>0.05). There were PDE5A1 and PDE5A2 mRNA expressions in rat corpus 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.

Key words

penis erectile dysfunction icariin nitric oxide phosphodiesterase type 5 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McDonald L G, Murad F. Nitric oxide and cyclic GMP signaling. Proc Soc Exp Biol Med, 1996,211(1):1–6PubMedGoogle Scholar
  2. 2.
    Murad F. Cyclic GMP: synthesis, metabolism, and function. Introduction and some historical comments. Adv Pharmacol, 1994,26:1–5PubMedGoogle Scholar
  3. 3.
    Andersson K E, Holmquist F. Regulation of tone in penile cavernous smooth muscle. Established concepts znd new findings. World J Urol, 1994, 12:249–261PubMedGoogle Scholar
  4. 4.
    Wang C L, Li Y, Wang Y X. Advances in the research of icariin and its active parts. J Chin TCM (Chinese), 1998,23(3):183–185Google Scholar
  5. 5.
    Jeremy J Y, Ballard S A, Naylor A M et al. Effects OF Sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. British J Urol, 1997, 79: 958–952Google Scholar
  6. 6.
    Lin C S, Lin G, Lue T F. Isolation of two isoforms of phosphodiesterase 5 from rat penis. Intl J Impotence Res, 2003, 15,129–136CrossRefGoogle Scholar
  7. 7.
    Francis S H, Turko I V, Corbin J D. Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol, 2001,65:1–52PubMedCrossRefGoogle Scholar
  8. 8.
    Soderling S H, Beavo J A. Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr Opin Cell Biol, 2000,12:174–179PubMedCrossRefGoogle Scholar
  9. 9.
    Kuthe A. Expression of different phophodiesterase genes in human cavernous smooth muscle. J Urol, 2001,165:280–283PubMedCrossRefGoogle Scholar
  10. 10.
    Corbin J D, Francis S H, Webb D J. Phosphdiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology, 2002,60:4–11PubMedCrossRefGoogle Scholar
  11. 11.
    Lin C S, Lau A, Tu R et al. Expression of three isoforms of cGMP-biding cGMP-Specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Commun, 2000,268:628–635PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2006

Authors and Affiliations

  • Jiang Zhaojian  (蒋兆健)
    • 1
    • 2
  • Hu Benrong  (胡本容)
    • 1
  • Wang Jialing  (王嘉陵)
    • 1
  • Tang Qiang  (汤强)
    • 1
  • Tan Yan  (谭艳)
    • 1
  • Xiang Jizhou  (向继洲)
    • 1
  • Liu Juyan  (刘菊妍)
    • 2
  1. 1.Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Guangzhou Hanfang Natural Medicine Research & Development Co., Ltd GuangzhouChina

Personalised recommendations