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  • 1
    In: BJU International, December 2012, Vol.110(11c), pp.E1196-E1201
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.11529.x/abstract Byline: George T. Kedia(1), Joachim E. Sonnenberg(2), Markus A. Kuczyk(1), Stefan Uckert(1) Keywords: prostate smooth muscle; arginase enzymes; nitric oxide (NO); cyclic GMP What's known on the subject? and What does the study add? A previous study by Lexander et al. in 2005, using two-dimensional gel electrophoresis, demonstrated the expression of arginase type II in the different anatomical regions of the prostate; however, to date, no study has addressed, using an in vitro approach, the role of arginase isoenzymes in the human prostate. The results of the present study demonstrate that: both arginase isoenzymes, Arg I and Arg II, are expressed in the transition zone of the human prostate; the inhibition of arginase antagonized, to a certain degree, the tension brought about by noradrenaline in isolated human prostate tissue; exposure of human prostate tissue to arginase inhibitors enhanced the local production of cyclic GMP; and inhibition of arginase enzymes in the human prostate may augment the activity of the nitric oxide/cyclicGMP pathway. OBJECTIVE To investigate the expression of arginase isoenzymes type I (Arg I) and type II (Arg II) in the transition zone of the human prostate and the functional significance of arginase enzymes in the control of prostate smooth muscle. MATERIALS AND METHODS Human prostate tissue was obtained from male patients who had undergone pelvic surgery. The expression of Arg I and Arg II was investigated using Western blot analysis. Using the organ bath technique, the effects of cumulative administration of difluoromethylornithine (DFMO), H-Orn-OH x HCl, H-Ile-OH and N-I-hydroxy-nor-L-arginine (nor-NOHA; 1 nM-10 A[micro]M) on the tension induced by noradrenaline in isolated prostate tissue were assessed. Tissue strips were also exposed to arginase inhibitors and the production of cyclic GMP was determined. RESULTS Western blot analysis showed the expression of Arg I and Arg II in the transition zone of the prostate. The tension induced by noradrenaline was antagonized by the drugs in the following rank order of efficacy: H-Orn-OH x HCl a[yen] H-Ile-OH a[yen] DFMO 〉 nor-NOHA; however, the maximum reversion of tension recorded ranged from only -25 to -13%. The enhancement in cyclic GMP production registered in the presence of the arginase inhibitors ranged from four- to 14-fold. CONCLUSIONS Arg I and Arg II are expressed in the transition zone of the human prostate. Isometric tension studies and measurement of cyclic GMP showed that inhibition of arginase can reverse, to a certain degree, the tension of human prostate tissue induced by the activation of [alpha]-adrenoceptors and enhance the accumulation of cyclic GMP. Future studies should explore further the role of arginase enzymes in the relaxation mediated by nitric oxide in prostate smooth muscle. Author Affiliation: (1)Hannover Medical School, Division of Surgery, Department of Urology and Urological Oncology, Hannover, and (2)Institute for Biochemical Research and Analysis, Urological Research Unit, Barsinghausen, Germany Correspondence: (*) George T. Kedia, Hannover Medical School, Division of Surgery, Department of Urology and Urological Oncology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. e-mail: kedia.george@mh-hannover.de Accepted for publication 1 June 2012 CAPTION(S): Supporting info item Supporting info item Supporting info item Supporting info item Supporting info item Supporting info item
    Keywords: Prostate Smooth Muscle ; Arginase Enzymes ; Nitric Oxide No ; Cyclic Gmp
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 2
    Language: English
    In: Urology, October 2012, Vol.80(4), pp.952.e9-952.e14
    Description: To investigate further the potential significance of the cyclic adenosine monophosphate (cAMP) pathway in the control of prostate smooth muscle. The cAMP pathway has been assumed to be an alternative pharmacologic target to treat dysfunctions of the human lower urinary tract. To date, only a few studies have addressed the physiologic relevance of cAMP signal transduction in the control of human prostate function. Phosphodiesterase activity was isolated from microsomal fractions prepared from prostatic tissue and subjected to biochemical analysis. Using the organ bath technique, the effects of the phosphodiesterase type (PDE)4 inhibitors Ro 20-1724, rolipram, and RP 73401 on the tension induced by norepinephrine of isolated prostatic tissue were investigated and compared with the PDE5 inhibitor sildenafil and BAY 13-1197, a nitric oxide-independent activator of the soluble guanylyl cyclase. Statistical analysis was conducted using the Gosset test. Biochemical analysis of the microsomal fraction revealed only a single peak of PDE activity that was sensitive to papaverine and the PDE4 inhibitors rolipram and Ro 20-1724. The tension induced by norepinephrine was reversed by the drugs with the following order of efficacy: Ro 20-1724, RP 73401, rolipram, sildenafil, and BAY 13-1197. Pre-exposure of the tissue to a threshold concentration (0.05 μM) of forskolin (adenlyl cyclase activator) increased the reversion of tension induced by rolipram and RP 73401 and the PDE5 inhibitor sildenafil. These results have provided evidence for the significance of cAMP signaling in the control of prostate smooth muscle.
    Keywords: Medicine
    ISSN: 0090-4295
    E-ISSN: 1527-9995
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  • 3
    Language: English
    In: Urology, December 2013, Vol.82(6), pp.1451.e13-1451.e19
    Description: To elucidate the functional responses of isolated human urethral smooth muscle to various agents known to exert smooth muscle contraction or relaxation. Specimens of penile urethra were obtained from male patients who had undergone male-to-female gender reassignment surgery. Using the tissue bath technique, the contraction induced by increasing concentrations (1 nM-10 μM) of norepinephrine, phenylephrine, acetylcholine, carbachol, prostaglandin F , endothelin 1, angiotensin II, and oxytocin was measured. In another set-up, the effects of C-type natriuretic peptide (0.1 nM-1 μM), sodium nitroprusside, sildenafil, forskolin, alpha -antagonist delquamine, and acetylcholine (1 nM/10 nM-10 μM) on the tension induced by norepinephrine were investigated. The production of cyclic guanosine monophosphate (GMP) and cyclic adenosine monophosphate (AMP) was measured by means of specific radioimmunoassays. Endothelin 1, oxytocin, prostaglandin F , norepinephrine, and phenylephrine induced dose-dependent contraction of the isolated urethral tissue, whereas acetylcholine, carbachol, and angiotensin II had no or only minor contractile effects. The contraction induced by norepinephrine was reversed by the drugs with the following rank order of efficacy: sodium nitroprusside 〉 delquamine 〉 sildenafil 〉 C-type natriuretic peptide 〉 forskolin 〉 acetylcholine. The maximal reversion of tension ranged from 68% (sodium nitroprusside) to 22% (acetylcholine). The relaxing effects of the drugs were paralleled by a several-fold increase in tissue levels of cyclic GMP and cyclic adenosine monophosphate. The results provide evidence that urethral smooth muscle is under the control of endogenous compounds, such as adrenergic agonists (norepinephrine and phenylephrine), vasoactive peptides, prostagladins, NO/cyclic GMP, and acetylcholine, assumed to influence micturition at the peripheral level.
    Keywords: Medicine
    ISSN: 0090-4295
    E-ISSN: 1527-9995
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  • 4
    Language: English
    In: The Journal of Urology, April 2015, Vol.193(4), pp.e633-e633
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2015.02.1734 Byline: Stefan Uckert Author Affiliation: Hannover, Germany Article Note: (footnote) Source of Funding: none
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 5
    Language: English
    In: The Journal of Urology, April 2011, Vol.185(4), pp.e91-e91
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 6
    Language: English
    In: The Journal of Urology, April 2017, Vol.197(4), pp.e218-e218
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2017.02.609 Byline: Stefan Ueckert Author Affiliation: Hannover, Germany Article Note: (footnote) Source of Funding: none
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 7
    Language: English
    In: The Journal of Urology, April 2011, Vol.185(4), pp.e300-e300
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 8
    Language: English
    In: The Journal of Urology, April 2018, Vol.199(4), pp.e583-e583
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 9
    Language: English
    In: The Journal of Urology, April 2018, Vol.199(4), pp.e584-e584
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 10
    Language: English
    In: The Journal of Urology, April 2011, Vol.185(4), pp.e300-e301
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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