Abstract
Introduction
Benign prostatic hyperplasia causes partial bladder outlet obstruction (pBOO), and many patients with pBOO are affected by not only voiding symptoms but also storage symptoms. We previously suggested that enhancement of 5-hydroxytryptamine (5-HT)-induced bladder contraction in the pBOO bladder may be one cause of storage symptoms. However, little is known about the presence of 5-HT in rat bladders. In this study, we hypothesized that mast cells are a source of 5-HT and investigated the distribution of mast cells and 5-HT in the bladders of rats with pBOO.
Methods
The bladders of female Sprague–Dawley rats were subjected to pBOO and sham operations for 1 week, were isolated, and were fixed for light or electron microscopy. Mast cells and 5-HT in the bladders were detected by toluidine blue staining and immunohistochemical staining, respectively. The mast cells were counted under a light microscope. Degranulated mast cells were observed under an electron microscope and counted under a light microscope.
Results
Mast cells were present in the mucosa/submucosa region in sham rat bladders. Their number was increased in the detrusor muscle/subserosa/serosa region, especially the subserosal layer, in pBOO rat bladders. The localization of mast cells almost matched that of 5-HT-positive cells in consecutive sections. Degranulated mast cells were present in sham and pBOO rat bladders, but the proportion of degranulated mast cells was significantly increased in every region in pBOO rat bladders compared with that in sham rat bladders.
Conclusion
These results suggest that mast cells contain 5-HT and are more abundant locally in the subserosal layer of pBOO rat bladders. 5-HT released from mast cells could stimulate 5-HT2 receptors on the detrusor muscle, and this may underlie storage symptoms.
Funding
Asahi Kasei Pharma Corp.
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Acknowledgments
Sponsorship and article processing charges for this study were funded by a consignment study of Asahi Kasei Pharma Corporation, Tokyo, Japan. We are grateful to Dr. Masahito Kawatani for providing helpful suggestions. Sponsorship for this study was funded by Asahi Kasei Pharma Corporation. Daniel McGowan and Springer Healthcare provided assistance with English language editing. Support for this assistance was funded by Asahi Kasei Pharma Corporation.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
This supplement was supported by Asahi Kasei Pharma Corp. Prior to peer review, Asahi Kasei Pharma Corp were offered the opportunity to review this paper for scientific accuracy. No changes were made as a result.
Disclosures
Mai Michishita, Ken-ichi Tomita, Kazuo Yano, and Ken-ichi Kasahara are employees of Asahi Kasei Pharma Corporation.
Compliance with ethics guidelines
All animal experiments were approved by the Committee on Ethics in Animal Experiments of Asahi Kasei Pharma Corporation. Female Sprague–Dawley rats were obtained from Charles River Laboratories (Tokyo, Japan). Rats were housed in an air conditioned room and fed a standard laboratory diet (CRF-1; Oriental Yeast, Tokyo, Japan). Studies were conducted in rats aged 8–11 weeks and weighing 180–250 g. All institutional and national guidelines for the care and use of laboratory animals were followed.
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Michishita, M., Tomita, Ki., Yano, K. et al. Mast Cell Accumulation and Degranulation in Rat Bladder with Partial Outlet Obstruction. Adv Ther 32 (Suppl 1), 16–28 (2015). https://doi.org/10.1007/s12325-015-0243-z
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DOI: https://doi.org/10.1007/s12325-015-0243-z