Cell and Tissue Research

, Volume 379, Issue 2, pp 373–387 | Cite as

Contractile elements and their sympathetic regulations in the pig urinary bladder: a species and regional comparative study

  • Retsu MitsuiEmail author
  • Ken Lee
  • Aoi Uchiyama
  • Shunta Hayakawa
  • Fumio Kinoshita
  • Shunichi Kajioka
  • Masatoshi Eto
  • Hikaru Hashitani
Regular Article


Contractile behaviour of the urinary bladder and its sympathetic inhibition during storage phases are not well understood. Here, we explore muscularis mucosae (MM) as a predominant mucosal contractile element and the capability of sympathetic nerves to relax detrusor smooth muscle (DSM) or MM. Distribution of α-smooth muscle actin (α-SMA)-immunoreactive cells was compared in pig, human, guinea pig, rat and mouse bladders by immunohistochemistry, while contractility of the bladder mucosa was compared in these species by isometric tension recordings. In pig, human and guinea pig bladders, DSM and MM located in the lamina propria expressed α-SMA immunoreactivity, while both rat and mouse bladders lacked a MM. Consistent with this presence or absence of MM, bladder mucosa of pig, human and guinea pig but not rat and mouse developed spontaneous phasic contractions (SPCs). Distribution of tyrosine hydroxylase (TH)-immunoreactive sympathetic nerve fibres was compared in pig DSM, MM, trigone and urethra, as were their sympathetic nerve-evoked contractile/relaxing responses examined. In pig DSM or MM, where TH-immunoreactive sympathetic fibres exclusively projected to the vasculature, sympathetic relaxations were difficult to demonstrate. In contrast, sympathetic contractions were invariably evoked in pig trigone and urethra where the smooth muscle cells receive TH-immunoreactive sympathetic innervations. Thus, SPCs of bladder mucosa appear to predominantly arise from the MM displaying species differences. Despite the currently accepted concept of sympathetic nerve-mediated DSM relaxation during the storage phase, it is unlikely that neurally released noradrenaline acts on β-adrenoceptors to relax either DSM or MM due to the anatomical lack of sympathetic innervation.


Urinary bladder Muscularis mucosae Trigone Urethra Smooth muscle Sympathetic nerve 



α-Smooth muscle actin


Detrusor smooth muscle


Electrical filed stimulation


Muscularis mucosae


Physiological salt solution


Smooth muscle cell


Spontaneous phasic contraction


Tyrosine hydroxylase



The authors wish to thank Dr. Richard Lang (Monash University) for his critical reading of the manuscript and are also grateful to Drs Akito Yamaguchi and Shinji Kono (Harasanshin Hospital) for providing human bladder specimens.


The present study was partly supported by Grant-in-Aid for Young Scientists (B) (No. 16K19361) from Japan Society for Promotion of the Science (JSPS) to R.M. and Grant-in-Aid for Scientific Research (C) (No. 17K11187) from JSPS to H.H.

Compliance with ethical statements

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical approval

The experimental protocols used in the present study were approved by the animal experimentation ethics committee at Nagoya City University Graduate School of Medical Sciences (No. H-28M-07) and the Ethics Committees of the Graduate School of Medical Sciences, Kyushu University and Harasanshin Hospital (No. 28-54). All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments.

Informed consent

All subjects gave written informed consent.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Retsu Mitsui
    • 1
    Email author
  • Ken Lee
    • 2
  • Aoi Uchiyama
    • 1
  • Shunta Hayakawa
    • 1
  • Fumio Kinoshita
    • 3
  • Shunichi Kajioka
    • 4
  • Masatoshi Eto
    • 2
  • Hikaru Hashitani
    • 1
  1. 1.Department of Cell PhysiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
  2. 2.Department of Urology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of Applied Urology and Molecular MedicineKyushu UniversityFukuokaJapan

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