Functional, Morphological And Molecular Characterization Of Bladder Dysfunction In Streptozotocin-induced Diabetic Mice: Evidence Of A Role For L-type Voltage-operated Ca 2+ Channels

dc.creatorLeiria L.O.S.
dc.creatorMonica F.Z.T.
dc.creatorCarvalho F.D.G.F.
dc.creatorClaudino M.A.
dc.creatorFranco-Penteado C.F.
dc.creatorSchenka A.
dc.creatorGrant A.D.
dc.creatorDe Nucci G.
dc.creatorAntunes E.
dc.date2011
dc.date2015-06-30T20:35:18Z
dc.date2015-11-26T14:51:37Z
dc.date2015-06-30T20:35:18Z
dc.date2015-11-26T14:51:37Z
dc.date.accessioned2018-03-28T22:03:17Z
dc.date.available2018-03-28T22:03:17Z
dc.identifier
dc.identifierBritish Journal Of Pharmacology. , v. 163, n. 6, p. 1276 - 1288, 2011.
dc.identifier71188
dc.identifier10.1111/j.1476-5381.2011.01311.x
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-79959745454&partnerID=40&md5=fd712076bbe7cc4904a038136c1f91b3
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/108518
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/108518
dc.identifier2-s2.0-79959745454
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1254536
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 Ca 2+ influx through L-type voltage-operated Ca 2+ channels (L-VOCC). EXPERIMENTAL APPROACH Male C57BL/6 mice were injected with streptozotocin (125 mg·kg -1). Four weeks later, contractile responses to carbachol, α,β-methylene ATP, KCl, extracellular Ca 2+ 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, α,β-methylene ATP, KCl, extracellular Ca 2+ 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 Ca 2+ influx through L-VOCC. © 2011 The British Pharmacological Society.
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dc.languageen
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dc.relationBritish Journal of Pharmacology
dc.rightsfechado
dc.sourceScopus
dc.titleFunctional, Morphological And Molecular Characterization Of Bladder Dysfunction In Streptozotocin-induced Diabetic Mice: Evidence Of A Role For L-type Voltage-operated Ca 2+ Channels
dc.typeArtículos de revistas


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