PMID- 17120748 OWN - NLM STAT- MEDLINE DCOM- 20080606 LR - 20211103 IS - 1672-0733 (Print) IS - 1672-0733 (Linking) VI - 26 IP - 4 DP - 2006 TI - Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penile cavernosum. PG - 460-2 AB - 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) micromol/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. FAU - Jiang, Zhaojian AU - Jiang Z AD - Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Hu, Benrong AU - Hu B FAU - Wang, Jialing AU - Wang J FAU - Tang, Qiang AU - Tang Q FAU - Tan, Yan AU - Tan Y FAU - Xiang, Jizhou AU - Xiang J FAU - Liu, Juyan AU - Liu J LA - eng PT - Journal Article PL - China TA - J Huazhong Univ Sci Technolog Med Sci JT - Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban JID - 101169627 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Flavonoids) RN - 0 (RNA, Messenger) RN - E0399OZS9N (Cyclic AMP) RN - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5) RN - EC 3.1.4.35 (Pde5a protein, rat) RN - H2D2X058MU (Cyclic GMP) RN - VNM47R2QSQ (icariin) SB - IM MH - Animals MH - Cyclic AMP/metabolism MH - Cyclic GMP/*metabolism MH - Cyclic Nucleotide Phosphodiesterases, Type 5/*biosynthesis/genetics MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/pharmacology MH - Flavonoids/*pharmacology MH - In Vitro Techniques MH - Male MH - Penis/*drug effects/metabolism MH - RNA, Messenger/genetics/metabolism MH - Rabbits MH - Radioimmunoassay MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2006/11/24 09:00 MHDA- 2008/06/07 09:00 CRDT- 2006/11/24 09:00 PHST- 2006/11/24 09:00 [pubmed] PHST- 2008/06/07 09:00 [medline] PHST- 2006/11/24 09:00 [entrez] AID - 10.1007/s11596-006-0421-y [doi] PST - ppublish SO - J Huazhong Univ Sci Technolog Med Sci. 2006;26(4):460-2. doi: 10.1007/s11596-006-0421-y.