Functional, morphological and molecular characterization of bladder dysfunction in streptozotocin-induced diabetic mice: evidence of a role for L-type voltage-operated Ca2+ channels

dc.creatorLeiria, LOS
dc.creatorMonica, FZT
dc.creatorCarvalho, FDGF
dc.creatorClaudino, MA
dc.creatorFranco-Penteado, CF
dc.creatorSchenka, A
dc.creatorGrant, AD
dc.creatorDe Nucci, G
dc.creatorAntunes, E
dc.date2011
dc.dateJUL
dc.date2014-07-30T17:47:14Z
dc.date2015-11-26T17:46:47Z
dc.date2014-07-30T17:47:14Z
dc.date2015-11-26T17:46:47Z
dc.date.accessioned2018-03-29T00:29:22Z
dc.date.available2018-03-29T00:29:22Z
dc.identifierBritish Journal Of Pharmacology. Wiley-blackwell, v. 163, n. 6, n. 1276, n. 1288, 2011.
dc.identifier0007-1188
dc.identifierWOS:000292098700017
dc.identifier10.1111/j.1476-5381.2011.01311.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/67687
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/67687
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1288594
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionBACKGROUND AND PURPOSE Diabetic cystopathy is one of the most common and incapacitating complications of diabetes mellitus. This study aimed to evaluate the functional, structural and molecular alterations of detrusor smooth muscle (DSM) in streptozotocin-induced diabetic mice, focusing on the contribution of Ca2+ influx through L-type voltage-operated Ca2+ channels (L-VOCC). EXPERIMENTAL APPROACH Male C57BL/6 mice were injected with streptozotocin (125 mg.kg(-1)). Four weeks later, contractile responses to carbachol, alpha,beta-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation were measured in urothelium-intact DSM strips. Cystometry and histomorphometry were performed, and mRNA expression for muscarinic M-2/M-3 receptors, purine P2X1 receptors and L-VOCC in the bladder was determined. KEY RESULTS Diabetic mice exhibited higher bladder capacity, frequency, non-void contractions and post-void pressure. Increased bladder weight, wall thickness, bladder volume and neural tissue were observed in diabetic bladders. Carbachol, alpha,beta-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation all produced greater DSM contractions in diabetic mice. The L-VOCC blocker nifedipine almost completely reversed the enhanced DSM contractions in bladders from diabetic animals. The Rho-kinase inhibitor Y27632 had no effect on the enhanced carbachol contractions in the diabetic group. Expression of mRNA for muscarinic M-3 receptors and L-VOCC were greater in the bladders of diabetic mice, whereas levels of M-2 and P2X1 receptors remained unchanged. CONCLUSIONS AND IMPLICATIONS Diabetic mice exhibit features of urinary bladder dysfunction, as characterized by overactive DSM and decreased voiding efficiency. Functional and molecular data suggest that overactive DSM in diabetes is the result of enhanced extracellular Ca2+ influx through L-VOCC.
dc.description163
dc.description6
dc.description1276
dc.description1288
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageen
dc.publisherWiley-blackwell
dc.publisherHoboken
dc.publisherEUA
dc.relationBritish Journal Of Pharmacology
dc.relationBr. J. Pharmacol.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectdiabetes
dc.subjectdetrusor smooth muscle
dc.subjectbladder dysfunction
dc.subjectL-type Ca2+ channels
dc.subjectRho-kinase
dc.subjectLower Urinary-tract
dc.subjectDetrusor Smooth-muscle
dc.subjectQuality-of-life
dc.subjectOutlet Obstruction
dc.subjectContractile Responses
dc.subjectOveractive Bladder
dc.subjectPurinoceptor Expression
dc.subjectMuscarinic Receptors
dc.subjectRho-kinase
dc.subjectRats
dc.titleFunctional, morphological and molecular characterization of bladder dysfunction in streptozotocin-induced diabetic mice: evidence of a role for L-type voltage-operated Ca2+ channels
dc.typeArtículos de revistas


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