Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/60012
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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampToque, Haroldo Alfredo Florespt_BR
dc.contributor.authorunicampDe Nucci, Gilbertopt_BR
dc.contributor.authorunicampAntunes, Edsonpt_BR
dc.typeArtigopt_BR
dc.titleIncreased cyclic guanosine monophosphate synthesis and calcium entry blockade account for the relaxant activity of the nitric oxide-independent soluble guanylyl cyclase stimulator BAY 41-2272 in the rabbit penile urethrapt_BR
dc.contributor.authorTeixeira, C.E.pt_BR
dc.contributor.authorToque, H.A.F.pt_BR
dc.contributor.authorDe Nucci, G.pt_BR
dc.contributor.authorAntunes, E.pt_BR
dc.subjectGuanilato ciclasept_BR
dc.subjectPiridinaspt_BR
dc.subjectÓxido nítricopt_BR
dc.subject.otherlanguageGuanylate cyclasept_BR
dc.subject.otherlanguageNitric oxidept_BR
dc.subject.otherlanguagePyridinespt_BR
dc.description.abstractTo study the direct relaxant activity of 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-4-ylamine (BAY 41-2272) in the rabbit penile urethra and to investigate its modulatory effect on nitric oxide (NO)-mediated responses. METHODS Urothelium-intact (U+) and denuded (U-) rings were mounted in 10-mL organ baths for isometric force recording. Intracellular cyclic guanosine monophosphate (cGMP) levels were quantified with specific kits. RESULTS BAY 41-2272 (0.0001 to 10 mu mol/L) caused relaxation of urethral rings contracted with phenylephrine (10 mu mol/L), with higher potency (P < 0.01) in U+ (pEC(50) 7.77 +/- 0.09) compared with U- (pEC(50) 6.84 +/- 0.19) preparations. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (100 mu mol/L) or the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ) (10 mu mol/L) had no effect on BAY 41-2272 responses in U+ or U- rings. The phosphodiesterase-5 inhibitor vardenafil (0.1 mu mol/L) potentiated the relaxant effects of BAY 41-2272 in both U+ (10-fold) and U- (sevenfold) tissues. Ca(2+)-induced contractions in K(+) depolarized rings were significantly attenuated by BAY 41-2272(1 mu mol/L) in an ODQ-insensitive manner. BAY 41-2272 (0.03-0.3 mu mol/L) increased the amplitude and duration of electrical field stimulation-induced relaxations (1 to 32 Hz), as well as those evoked by the NO donor glyceryl trinitrate (0.0001 to 10 mu mol/L). BAY 41-2272 induced ODQ-resistant increases in cGMP levels above baseline (approximately twofold) in both U + and U- rings. CONCLUSIONS BAY 41-2272 relaxes penile urethra in a synergic fashion with NO. Targeting soluble guanylate cyclase with BAY 41-2272 may represent a new therapy in the management of voiding disturbances associated with impaired NO-cGMP signalingpt
dc.description.eventElsevierpt_BR
dc.relation.ispartofUrologypt_BR
dc.relation.ispartofabbreviationUrologypt_BR
dc.publisher.cityNew York, NYpt_BR
dc.publisher.countryEstados Unidospt_BR
dc.publisherElsevierpt_BR
dc.date.issued2008pt_BR
dc.date.monthofcirculationSept.pt_BR
dc.identifier.citationUrology. Elsevier Science Inc, v. 72, n. 3, n. 711, n. 715, 2008.pt_BR
dc.language.isoengpt_BR
dc.description.volume72pt_BR
dc.description.issuenumber3pt_BR
dc.description.firstpage711pt_BR
dc.description.lastpage715pt_BR
dc.rightsfechadopt_BR
dc.sourceWOSpt_BR
dc.identifier.issn0090-4295pt_BR
dc.identifier.eissn1527-9995pt_BR
dc.identifier.doi10.1016/j.urology.2007.12.031pt_BR
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0090429507026027pt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPpt_BR
dc.description.sponsorship1FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOpt_BR
dc.description.sponsordocumentnumbersem informaçãopt_BR
dc.date.available2014-07-30T14:33:09Z
dc.date.available2015-11-26T16:53:58Z-
dc.date.accessioned2014-07-30T14:33:09Z
dc.date.accessioned2015-11-26T16:53:58Z-
dc.description.provenanceMade available in DSpace on 2014-07-30T14:33:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2008 Bitstreams deleted on 2020-05-18T20:41:04Z: WOS000259853800070.pdf,. Added 1 bitstream(s) on 2020-05-19T14:30:52Z : No. of bitstreams: 2 000259853800070.pdf: 346119 bytes, checksum: 183e78d60e32e296c168624a2b59dd9b (MD5) WOS000259853800070.pdf.txt: 24264 bytes, checksum: 74692f7db31fe22cdcd596f537f084fe (MD5)en
dc.description.provenanceMade available in DSpace on 2015-11-26T16:53:58Z (GMT). No. of bitstreams: 2 WOS000259853800070.pdf: 270035 bytes, checksum: 4331479a12580fe9d8747586f629d735 (MD5) WOS000259853800070.pdf.txt: 24264 bytes, checksum: 74692f7db31fe22cdcd596f537f084fe (MD5) Previous issue date: 2008en
dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60012
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60012-
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.unidadeFaculdade de Ciências Médicaspt_BR
dc.identifier.source000259853800070-
dc.creator.orcid0000-0002-8426-3136pt_BR
dc.creator.orcid0000-0002-4346-7941pt_BR
dc.creator.orcid0000-0003-2201-8247pt_BR
dc.type.formArtigo originalpt_BR
dc.description.eventsponsorNew York, NYpt_BR
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