887 THE POTENTIAL ROLE OF SIALORPHIN IN MEDIATING UROGENITAL SYMPTOMS IN DIABETES

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2010887 THE POTENTIAL ROLE OF SIALORPHIN IN MEDIATING UROGENITAL SYMPTOMS IN DIABETES Giulia Calenda, Nirmala Kanika, Sylvia Suadicani, Moses Tar, Dwaraka Kuppam, David Spray, Arnold Melman, and Kelvin Davies Giulia CalendaGiulia Calenda More articles by this author , Nirmala KanikaNirmala Kanika More articles by this author , Sylvia SuadicaniSylvia Suadicani More articles by this author , Moses TarMoses Tar More articles by this author , Dwaraka KuppamDwaraka Kuppam More articles by this author , David SprayDavid Spray More articles by this author , Arnold MelmanArnold Melman More articles by this author , and Kelvin DaviesKelvin Davies More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1643AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes is associated with the development of urogenital complications such as erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). It remains to be determined if ED and LUTS have an underlying common molecular mediator. We have previously demonstrated that diabetes results in down regulation of the Vcsa1 gene expression in corporal smooth muscle. Sialorphin, the protein product of Vcsa1, acts as a potent endogenous inhibitor of neutral endopeptidase (NEP) and has been shown to play an important role in erectile physiology by modulating corporal smooth muscle tone. Because sialorphin is released into the circulation it could also act on non-corporal smooth muscle tissue, such as the bladder. The work described here investigated if diabetes results in lowered circulating sialorphin levels, and if changes in sialorphin levels could have a similar impact on the biochemistry of distinct urogenital tissues. METHODS Diabetes was induced in Sprague-Dawley rat using streptozotocin (STZ). The levels of sialorphin in the serum of age matched controls (AMC), STZ-diabetic and STZ-diabetic rats treated with insulin were determined by radioimmunoassay (RIA). The effect of sialorphin on intracellular calcium ([Ca2+]i) was determined in cultured bladder and corporal smooth muscle cells from diabetic and non-diabetic rats using calcium imaging. RESULTS Circulating levels of sialorphin are decreased in diabetic rats by approximately 35±3.6%. In insulin treated STZ-diabetic animals circulating levels of sialorphin were not significantly different from AMC (87±3.4% of AMC). In vitro we demonstrate that sialorphin potentiates the Ca2+- releasing effect of bradykinin in both bladder (by about 73±8.9%) and corporal (by about 40±6.3%) smooth muscle cells, probably through the inhibition of NEP-mediated degradation of bradykinin. CONCLUSIONS In this study we show that diabetes is associated with a decrease of circulating sialorphin in rats. In addition sialorphin acts to modulate [Ca2+]i in both corporal and bladder smooth muscle cells, probably though its actions as a very effective NEP inhibitor. Intracellular calcium is an important mediator of smooth muscle tone, which in turn is an important determinant of both erectile and bladder function. Our work suggests that the down regulation of circulating sialorphin levels which occur with diabetes acts as a common factor for the development of LUTS in diabetes. Bronx, NY© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e347 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giulia Calenda More articles by this author Nirmala Kanika More articles by this author Sylvia Suadicani More articles by this author Moses Tar More articles by this author Dwaraka Kuppam More articles by this author David Spray More articles by this author Arnold Melman More articles by this author Kelvin Davies More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...