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Detrusor Smooth Muscle (detrusor + smooth_muscle)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Effects of imatinib mesylate (Glivec®) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder

NEUROUROLOGY AND URODYNAMICS, Issue 3 2006
Yasue Kubota
Abstract Aims In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. Methods Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. Results Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 ,M) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 ,M) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. Conclusions The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source]

Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstruction

NEUROUROLOGY AND URODYNAMICS, Issue 2 2006
Edward LaBelle
Abstract Aims Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. Methods Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits. Results The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 µM. Conclusions The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source]

Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscle

NEUROUROLOGY AND URODYNAMICS, Issue 1 2006
Anita S. Mannikarottu
Abstract Aims Obstruction of the urinary bladder outlet induces detrusor smooth muscle (DSM) hypertrophy. The goal of this study was to determine whether the composition of thin filament-associated proteins, known to play important roles in cytoskeletal structure and/or the regulation of contraction, is altered in DSM during hypertrophy. Methods DSM hypertrophy was induced in male rabbits by partial ligation of the urethra. Sham-operated rabbits served as a control. Reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR revealed a significant increase in the expression of mRNAs for basic (h1) calponin (CaP), and ,-isoform of tropomyosin (Tm) in hypertrophied DSM compared to controls. Western blotting and two-dimensional (2-D) gel electrophoresis showed enhanced expression of these proteins and also a significant increase in the expression of ,-non muscle and ,-smooth muscle actin in the DSM from obstructed bladders, while ,-actin remained constant. Results Enhanced expression of these proteins in the DSM from obstructed bladders was confirmed by immunofluorescence microscopy. Double immunostaining with Cap/Tm and ,/,-actin-specific antibodies showed co-localization of these proteins in myocytes. Colocalization of smooth muscle specific myosin and CaP to cytoplasmic filaments in cells dissociated from the hypertrophied DSM indicated that these cells are differentiated smooth muscle cells. Conclusions The change in the isoforms of actin, Cap, and Tm may be part of the molecular mechanism for bladder compensation in increased urethral resistance. Neurourol. Urodynam. © 2005 Wiley-Liss, Inc. [source]

Evolving mechanisms of action of alverine citrate on phasic smooth muscles

BRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2007
M Hayase
Background and purpose: We have investigated the mechanisms underlying the paradoxical ability of the antispasmodic, alverine, to enhance spontaneous activity in smooth muscles while suppressing evoked activity. Experimental approach: The effects of alverine on spontaneous and induced contractile activity were examined in preliminary experiments with various smooth muscles. More detailed effects were also investigated by recording membrane potential, intracellular Ca2+ concentration ([Ca2+]i) and tension from single-bundle detrusor smooth muscle (DSM) of the guinea-pig urinary bladder. Key results: Alverine (10 ,M) increased the frequency and amplitude of spontaneous action potentials, transient increases in [Ca2+]i and associated contractions. Alverine also decreased action potential rate of decay, suggesting inhibition of L -type Ca channel inactivation. Charybdotoxin (50 nM) but neither cyclopiazonic acid (10 ,M) nor Bay K 8644 (10 ,M) attenuated alverine-induced enhancement of spontaneous contractions. Alverine suppressed contractions produced by high K (40 mM) or ACh (10 ,M), without affecting electrical responses and with little suppression of increases in [Ca2+]i. This feature was very similar to that of the effects of the Rho kinase inhibitor Y-27632 (10 ,M). Conclusions and implications: Alverine may increase Ca influx during action potentials due to inhibition of the inactivation of L -type Ca channels, but may also suppress evoked activity by inhibiting the sensitivity of contractile proteins to Ca2+. The proportional contribution of Ca-dependent and Ca-independent contractions in DSM may differ between spontaneous and evoked activity, necessitating further investigations into the interactions between these pathways for assessing the therapeutic potential of alverine to treat DSM dysfunction. British Journal of Pharmacology (2007) 152, 1228,1238; doi:10.1038/sj.bjp.0707496; published online 15 October 2007 [source]