No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Sep 2000RABBIT CORPUS CAVERNOSUM SMOOTH MUSCLE SHOWS A DIFFERENT PHOSPHODIESTERASE PROFILE THAN HUMAN CORPUS CAVERNOSUM YUHONG QIU, PATRICIA KRAFT, ELIZABETH LOMBARDI, and JOANNA CLANCY YUHONG QIUYUHONG QIU More articles by this author , PATRICIA KRAFTPATRICIA KRAFT More articles by this author , ELIZABETH LOMBARDIELIZABETH LOMBARDI More articles by this author , and JOANNA CLANCYJOANNA CLANCY More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67331-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of cAMP/cGMP secondary messenger systems. Fluctuations in the level of cyclic nucleotides control the smooth muscle tone of corpus cavernosum. It had been shown that milrinone, a PDE3 inhibitor, was as potent as sildenafil, a PDE5 inhibitor, in relaxing human corpus cavernosum. However, milrinone is much less effective in relaxing rabbit corpus cavernosum than sildenafil. PDEs in rabbit corpus cavernosum were characterized and organ bath experiments were carried out in an attempt to search for the biochemical basis of this species difference. Materials and Methods: In a biochemical study, PDE isozymes from rabbit corpus cavernosum were isolated by FPLC and characterized by PDE assay. In organ bath experiments, rabbit corpus cavernous tissue strips were precontracted and increasing doses of various inhibitors were added. Results: The major PDE in rabbit corpus cavernosum is PDE5. There are small amounts of PDE2 and PDE1. PDE3, which contributes significantly to the total PDE activity in human corpus cavernosum, is apparently lacking in rabbit corpus cavernosum. Organ bath experiments with isotype-specific inhibitors confirm this conclusion. Conclusion: The distribution of PDE isozymes in corpus cavernosum is different in human and in rabbit. This could be the biochemical basis for the differential effects of milrinone in relaxing rabbit and human corpus cavernosum. Our study emphasizes the importance of a more complete understanding of the tissue distribution of targeted proteins in an animal model before applying the results to humans. References 1 : Physiol Rev1995; 75: 725. Google Scholar 2 : Biochem Biophys Res Comm1998; 246: 570. Google Scholar 3 : Biochem Biophys Res Comm1998; 250: 751. Google Scholar 4 : Proc Natl Acad Sci USA1998; 95: 8991. Google Scholar 5 : J Biol Chem1998; 273: 15559. Google Scholar 6 : J Biol Chem1998; 273: 15553. Google Scholar 7 : Proc Natl Acad Sci USA1999; 96: 7071. Google Scholar 8 : J Biol Chem1999; 274: 18438. Google Scholar 9 : Arch Biochem Biophys1995; 322: 1. Google Scholar 10 : J Biol Chem1993; 268: 6470. Google Scholar 11 : Int J Impotence Res1996; 8: 47. Google Scholar 12 : J Clin Invest1991; 88: 112. Google Scholar 13 : Science1992; 257: 401. Google Scholar 14 : J Urol1993; 149: 1246. Link, Google Scholar 15 : Circulation1993; 87: V30. Google Scholar 16 : J Urol1998; 159: 1390. Link, Google Scholar 17 : Biochemistry1971; 10: 311. Google Scholar 18 : Eur J Pharmacol1998; 349: 263. Google Scholar 19 : J Urol1992; 147: 220. Link, Google Scholar 20 : World J Urol1997; 15: 32. Google Scholar 21 : Mol Pharmacol1990; 37: 206. Google Scholar 22 : Br J Pharmacol1991; 102: 30P. Google Scholar 23 : J Pharmacol Exp Ther1993; 265: 1213. Google Scholar 24 : Methods Enzymol1988; 159: 489. Google Scholar 25 : Mol Pharmacol1994; 46: 399. Google Scholar 26 : Prostaglandins, Leukotrienes Essential Fatty Acids1999; 60: 111. Google Scholar From the Department of Reproductive Therapeutics, R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byKotera J, Mochida H, Inoue H, Noto T, Fujishige K, Sasaki T, Kobayashi T, Kojima K, Yee S, Yamada Y, Kikkawa K and Omori K (2018) Avanafil, a Potent and Highly Selective Phosphodiesterase-5 Inhibitor for Erectile DysfunctionJournal of Urology, VOL. 188, NO. 2, (668-674), Online publication date: 1-Aug-2012. Volume 164Issue 3 Part 1September 2000Page: 882-886 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordscorpus cavernosumphosphodiesterasedifferential distributionMetricsAuthor Information YUHONG QIU More articles by this author PATRICIA KRAFT More articles by this author ELIZABETH LOMBARDI More articles by this author JOANNA CLANCY More articles by this author Expand All Advertisement PDF downloadLoading ...