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MP26-19: Downregulation of monoamine oxidase A may contribute to development of detrusor hyper contractility in urinary bladder with partial bladder outlet obstruction in rats

Saturday, May 13
7:00 AM - 9:00 AM
Location: BCEC: Room 160

Presentation Authors: Mai Michishita, Izunokuni, Japan, Tsuyoshi Hattori*, Tokyo, Japan, Kazuo Yano, Ken-ichi Tomita, Ken-ichi Kasahara, Izunokuni, Japan

Introduction: In a previous study, 5-hydroxytryptamine (5-HT) was found to induce hyper contraction in urinary bladder strips in rats with partial bladder outlet obstruction (pBOO) and 5-HT was suggested to be a trigger of hyper contractility of the detrusor [Sakai T. et al. 2013]. To clarify whether 5-HT contributes to the development of detrusor overactivity and whether 5-HT turnover is involved in overactivity in vivo, we investigated the expression and activity of monoamine oxidase A (MAO-A), a 5-HT-metabolizing enzyme, in the urinary bladder in pBOO rats.

Methods: Forty-one Female Sprague Dawley rats (aged 8-11 weeks) were used; 12 rats for histology, and 29 rats for western blotting and MAO activity assay. pBOO was induced as described previously [Sakai T. et al. 2013]. At 3, 7, and 14 days after pBOO induction, animals were anesthetized, and urinary bladders were isolated and fixed for histology, or were stored at -80°C until use for western blotting and MAO activity assay to measure expression levels of MAO-A and activity of MAO, respectively. The distribution of MAO-A in the bladder was examined by immunohistochemistry. MAO activity was measured by MAO-Glo™ Assay. All values were expressed as means ± SEM. Statistical differences were determined by unpaired t-test using SAS System ver. 9.2 and EXSUS ver. 7.7.1. P values of <0.05 were considered significant.

Results: Expression levels of MAO-A/GAPDH decreased to 46.2 ± 2.7% on day 7 in rat bladders with pBOO (P<0.01) as compared to those in sham rats (Fig). MAO activity in rat urinary bladders also decreased to 48.9 ± 2.9% on day 7 pBOO (P<0.01) as compared to sham rats. The decrease in MAO activity persisted on day 14 (P<0.01). On immunohistochemistry, MAO-A-positive cells were predominantly observed in the detrusor layer in sham rat bladders. In pBOO rats, in contrast, the intensity of the MAO-A-positive signal decreased overall as compared to sham rats.

Conclusions: We demonstrated that the levels of MAO-A and activity of MAO decreased in the urinary bladder from pBOO rats as compared with sham rats. These results suggest that downregulation of 5-HT degradation leads to detrusor hypercontractility and/or facilitates hyper-contraction induced by 5-HT in the urinary bladder in pBOO rats.

Source Of Funding: Asahi Kasei Pharma Co.

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MP26-19: Downregulation of monoamine oxidase A may contribute to development of detrusor hyper contractility in urinary bladder with partial bladder outlet obstruction in rats



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