Gap junction expression and the effects of gap junction inhibitors in overactive bladder models: does ovariectomy have a role?

Babaoglu, Mehmet; Zümrütbaş, Ali Ersin; Acar, Ismail Cenk; Hatip, Funda Bölükbaşı; Küçükatay, Vural; Eskiçorapçı, Saadettin; Aybek, Zafer

doi:10.1007/s11255-013-0488-x

Cited by 8 publications

(6 citation statements)

References 17 publications

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“…29 In rats oxybutynin induced relaxant responses of partial BOO bladder 4 weeks postoperatively were significantly higher than in controls. 30 In cystitis we found that the responsiveness of detrusor muscle strips to CCh was decreased due to bladder wall thickening as a result of excessive build-up of type I collagen in the bladder. Our urodynamic recording, metabolic test and muscle strip contractility studies revealed that MK-801 treatment improved but could not completely reverse bladder function to the normal level.…”

Section: Discussionmentioning

confidence: 88%

Inhibition of NMDAR Reduces Bladder Hypertrophy and Improves Bladder Function in Cyclophosphamide Induced Cystitis

et al. 2015

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Purpose We examined the role of NMDAR in the regulation of bladder hypertrophy and function in a rat model of cyclophosphamide induced cystitis. Materials and Methods Cystitis was induced by intraperitoneal injection of cyclophosphamide (150 mg/kg body weight). NMDAR phosphorylation (activity) and signal transduction pathways were examined by direct measurement and by specific inhibitors in vivo. Bladder hypertrophy was measured by bladder weight/body weight and type I collagen expression. Bladder function was examined by metabolic recording, conscious cystometry and detrusor muscle strip contractility in response to carbachol. Results NMDAR activity measured by the phosphorylation level of the NMDAR1 (NR1) subunit was expressed in the spinal cord but not in the bladder at 48 hours of cystitis. NMDAR inhibition with dizocilpine (MK-801) reduced the cystitis induced increment of bladder weight and type I collagen up-regulation in the bladder. NMDAR regulated type I collagen up-regulation was mediated by the PI3K/Akt pathway. NMDAR inhibition also attenuated cystitis induced urinary frequency measured by metabolic cage and cystometry. Cystitis decreased the responsiveness of detrusor muscle strips to carbachol, which was reversed by MK-801 in vivo. Unlike MK-801 the NMDAR antagonist D-AP5, which could not block central NMDAR activity, had no effect on bladder hypertrophy, type I collagen up-regulation or Akt activation caused by cystitis in the bladder. Conclusions Findings suggest that NMDAR activity has a role in cystitis induced bladder hypertrophy and overactivity. NMDAR mediated Akt activation may underlie the mechanism of bladder dysfunction.

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Section: Discussionmentioning

confidence: 88%

Inhibition of NMDAR Reduces Bladder Hypertrophy and Improves Bladder Function in Cyclophosphamide Induced Cystitis

et al. 2015

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“…To determine whether GJIC was required for the increase of adriamycin-induced cytotoxicity in cells with GJIC, the breast cancer cells Hs578T and MCF-7 were treated with chemical modulators of GJs prior and during exposure to 6 µM adriamycin [inhibitor, oleamide (22,23) or 18-α-GA (24,25); potentiator, RA (21,26)] at high density (GJ formed) or low density (no GJ formed). Fig.…”

Section: Influence Of Gj Potentiator On the Cytotoxicity Of Adriamycinmentioning

confidence: 99%

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

Jiang

Dong

et al. 2016

Oncology Letters

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Abstract. Gap junctions (GJs) serve the principal role in the antineoplastic (cytotoxicity and induced apoptosis) effect of chemical drugs. The aim of the present study was to determine the effect of GJ intercellular communication (GJIC) composed of connexin 43 (Cx43) on adriamycin cytotoxicity in breast cancer cells. Four cell lines (Hs578T, MCF-7, MDA-MB-231 and SK-BR-3) with different degree of malignancy were used in the study. The results of western blotting and immunofluorescence revealed that, in Hs578T and MCF-7 cells, which have a low degree of malignancy, the expression levels of Cx43 and GJIC were higher than those in MDA-MB-231 and SK-BR-3 cells (which have a high degree of malignancy). In Hs578T and MCF-7 cells, where GJ could be formed, the function of GJ was modulated by a pharmacological potentiators [retinoid acid (RA)]/inhibitors [oleamide and 18-α-glycyrrhetinic acid (18-α-GA)] and small interfering RNA (siRNA). In high-density cells (where GJ was formed), enhancement of GJ function by RA increased the cytotoxicity of adriamycin, while inhibition of GJ function by oleamide/18-α-GA and siRNA decreased the cytotoxicity caused by adriamycin. Notably, the modulation of GJ did not affect the survival of cells treated with adriamycin when cells were in low density (no GJ was formed). The present study illustrated the association between GJIC and the antitumor effect of adriamycin in breast cancer cells. The cytotoxicity of adriamycin on breast cancer cells was increased when the function of gap junctions was enhanced.

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“…Gap junction blockers have previously been used on bladder tissue (Hashitani et al, 2001, 2004; Christ et al, 2003; Miyazato et al, 2006; Ikeda et al, 2007; Kim et al, 2011; Babaoglu et al, 2013). Similar effects have been found with 18α-GA and 18β-GA isomers (Miyazato et al, 2006; Ikeda et al, 2007; Kim et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Bladder Wall Micromotions Alters Intravesical Pressure Activity in the Isolated Bladder

et al. 2019

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Micromotions are phasic contractions of the bladder wall. During urine storage, such phasic activity has little effect on intravesical pressure, however, changed motile activity may underlie urodynamic observations such as detrusor overactivity. The potential for bladder motility to affect pressure reflects a summation of the overall movements, comprising the initiation, propagation, and dissipation components of micromotions. In this study, the influence of initiation of micromotions was investigated using calcium activated chloride channel blocker niflumic acid, and the effect of propagation using blockers of gap junctions. The overall bladder tone was modulated using isoprenaline. Isolated tissue strips and whole bladder preparations from juvenile rats were used. 18β-glycyrrhetinic acid was used to block gap junctions, reducing the amplitude and frequency of micromotions in in vitro and ex vivo preparations. Niflumic acid reduced the frequency of micromotions but had no effect on the amplitude of pressure fluctuations. Isoprenaline resulted in a reduction in pressure fluctuations and a decrease in pressure baseline. Using visual video data analysis, bladder movement was visible, irrespective of lack of pressure changes, which persisted during bladder relaxation. However, micromotions propagated over shorter distances and the overall bladder tone was reduced. All these results suggest that phasic activity of the bladder can be characterised by a combination of initiation and propagation of movement, and overall bladder tone. At any given moment, intravesical pressure recordings are an integration of these parameters. This synthesis gives insight into the limitations of clinical urodynamics, where intravesical pressure is the key indicator of detrusor activity.

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Gap junction expression and the effects of gap junction inhibitors in overactive bladder models: does ovariectomy have a role?

Cited by 8 publications

References 17 publications

Inhibition of NMDAR Reduces Bladder Hypertrophy and Improves Bladder Function in Cyclophosphamide Induced Cystitis

Inhibition of NMDAR Reduces Bladder Hypertrophy and Improves Bladder Function in Cyclophosphamide Induced Cystitis

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

Modulation of Bladder Wall Micromotions Alters Intravesical Pressure Activity in the Isolated Bladder

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