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, L O S
dc.creatorMónica, 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-Jul
dc.date2015-11-27T13:21:09Z
dc.date2015-11-27T13:21:09Z
dc.date.accessioned2018-03-29T01:12:40Z
dc.date.available2018-03-29T01:12:40Z
dc.identifierBritish Journal Of Pharmacology. v. 163, n. 6, p. 1276-88, 2011-Jul.
dc.identifier1476-5381
dc.identifier10.1111/j.1476-5381.2011.01311.x
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/21391978
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/199318
dc.identifier21391978
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1299551
dc.descriptionDiabetic 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). 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. 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. 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.
dc.description163
dc.description1276-88
dc.languageeng
dc.relationBritish Journal Of Pharmacology
dc.relationBr. J. Pharmacol.
dc.rightsfechado
dc.rights© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
dc.sourcePubMed
dc.subjectAmides
dc.subjectAnimals
dc.subjectCalcium Channel Blockers
dc.subjectCalcium Channels, L-type
dc.subjectCalcium Chloride
dc.subjectCarbachol
dc.subjectCholinergic Agonists
dc.subjectDiabetes Mellitus, Experimental
dc.subjectEnzyme Inhibitors
dc.subjectGene Expression Regulation
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57bl
dc.subjectNifedipine
dc.subjectPyridines
dc.subjectRna, Messenger
dc.subjectReceptor, Muscarinic M2
dc.subjectReceptor, Muscarinic M3
dc.subjectReceptors, Purinergic P2x1
dc.subjectUrinary Bladder Diseases
dc.subjectRho-associated Kinases
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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