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      The Relaxation Induced by Uroguanylin and the Expression of Natriuretic Peptide Receptors in Human Corpora Cavernosa

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          Abstract

          Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction. This study investigates the relaxant effects of the atrial natriuretic peptide (ANP) and uroguanylin (UGN), and expression of natriuretic peptide receptors on strips of human corpora cavernosa (HCC). Quantitative analysis of natriuretic receptor expression and relaxation of precontracted strips were used to assess the membrane-bound guanylate cyclase-cyclic guanosine monophosphate (cGMP) pathway in HCC strips. HCC was obtained from a cadaver donor at the time of collection of organs for transplantation (14-47 years) and strips were mounted in organ baths for isometric studies. ANP and UGN both induced concentration-dependent relaxation on HCC strips with a maximal response attained at 300 nM, corresponding to 45.4±4.0% and 49±4.8%, respectively. The relaxation is not affected by 30 µM 1H-[1,2,4]oxaolodiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylate cyclase inhibitor), but it is significantly blocked by 10 µM isatin, a nonspecific particulate guanylate cyclase (pGC) inhibitor. UGN was unable to potentiate electrical field stimulation (EFS) or acetylcholine-induced relaxations. The potential role of pGC activation and cGMP generation in this effect is reinforced by the potentiation of this effect by phosphodiesterase-5 inhibitor vardenafil (55.0±7.5-UGN vs. 98.6±1.4%-UGN+vardenafil; P<0.05). The relaxant effect was also partially (37.6%) blocked by the combination iberitoxin-apamin but was insensitive to glybenclamide. The expression of guanylate cyclase receptors (GC-A, GC-B, GC-C) and the expression of the natriuretic peptide "clearance" receptor (NPR-C) were confirmed by real-time polymerase chain reaction. The exposure of HCC strips to ANP (1 µM) and UGN (10 µM) significantly increased cGMP, but not cyclic adenosine monophosphate (cAMP) levels. UGN relaxes HCC strips by a guanylate cyclase and K(ca)-channel-dependent mechanism. These findings obtained in HCC reveal that the natriuretic peptide receptors are potential targets for the development of new drugs for the treatment of erectile dysfunction. © 2010 International Society for Sexual Medicine.

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          Author and article information

          Journal
          The Journal of Sexual Medicine
          The Journal of Sexual Medicine
          Wiley
          17436095
          November 2010
          November 2010
          : 7
          : 11
          : 3610-3619
          Article
          10.1111/j.1743-6109.2009.01672.x
          20102442
          d6e514b8-f77d-442e-b542-22ae7cd5985b
          © 2010

          https://www.elsevier.com/tdm/userlicense/1.0/

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