The relaxation induced by uroguanylin and the expression of natriuretic peptide receptors in human corpora cavernosa

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dc.contributor.authorSousa C.M.
dc.contributor.authorHavt A.
dc.contributor.authorSantos C.F.
dc.contributor.authorArnaud-Batista F.J.
dc.contributor.authorCunha K.M.A.
dc.contributor.authorCerqueira J.B.G.
dc.contributor.authorFonteles M.C.
dc.contributor.authorNascimento N.R.F.
dc.date.accessioned2024-03-13T01:32:51Z
dc.date.available2024-03-13T01:32:51Z
dc.date.issued2010
dc.description.abstractIntroduction. Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction. Aim. 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). Main Outcome Measures. 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. Methods. 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. Results. 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. Conclusions. UGN relaxes HCC strips by a guanylate cyclase and Kca-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.
dc.description.firstpage3610
dc.description.issuenumber11
dc.description.lastpage3619
dc.description.volume7
dc.identifier.doi10.1111/j.1743-6109.2009.01672.x
dc.identifier.issn1743-6109
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/37258
dc.relation.ispartofJournal of Sexual Medicine
dc.rightsAcesso Restrito
dc.subject.otherlanguageErectile Function
dc.subject.otherlanguageGuanylins
dc.subject.otherlanguageMembrane-Bound Guanylate Cyclase Receptors
dc.subject.otherlanguageNatriuretic Peptide and Physiology of Penile Erection
dc.titleThe relaxation induced by uroguanylin and the expression of natriuretic peptide receptors in human corpora cavernosa
dc.typeArtigo
local.scopus.citations14
local.scopus.eid2-s2.0-77955860989
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77955860989&origin=inward
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