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Roles of adenosine A1 and A2A receptors in the control of micturition in rats

Authors

  • Takeya Kitta,

    1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    2. Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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  • Michael B. Chancellor,

    1. Department of Urology, William Beaumont Hospital, Royal Oak, Michigan
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  • William C. de Groat,

    1. Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Sadako Kuno,

    1. Neuroscience Institute, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
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  • Katsuya Nonomura,

    1. Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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  • Naoki Yoshimura

    Corresponding author
    1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    2. Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • Correspondence to: Naoki Yoshimura, M.D., Ph.D., Department of Urology, University of Pittsburgh School of Medicine, Suite 700, Kaufmann Medical Bldg., 3471 Fifth Ave, Pittsburgh, PA 15213. E-mail: nyos@pitt.edu

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  • Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
  • The authors declare that they have no conflict of interest.
  • Author contributions: Takeya Kitta had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis. Kitta and Yoshimura conceptualized and designed the study, analyzed and interpreted the data and obtained funding. Yoshimura, Kitta, Chancellor, de Groat, Kuno, and Nonomura critically revised the manuscript for important intellectual content. The data were acquired by Kitta. He also drafted the manuscript, did the statistical analysis and provided administrative, technical, or material support. Supervision for the final approval of the version to be published was done by Yoshimura.

Abstract

Aims

Adenosine is a neurotransmitter that exerts numerous physiological effects in many organs. However, few studies have focused on the role of adenosine receptors in the control of micturition. Therefore, we examined the role of adenosine A1 and A2A receptors in the control of bladder activity in rats with normal or acetic acid (AA) irritated bladders.

Methods

Cystometrograms during saline or 0.2% AA infusion were recorded under urethane anesthesia in female Sprague–Dawley rats. After a stabilization period, CCPA (A1 receptor agonist) and/or ZM24138 (A2A receptor antagonist) were administered intravenously (i.v.), intrathecally (i.t.), intracerebroventricularly (i.c.v.), or intravesically. Micturition parameters were recorded and compared before and after drug administration.

Results

I.v., i.t., or i.c.v. administration of CCPA or ZM24138 significantly increased intercontraction intervals (ICIs) in both saline and AA infusion groups. During AA infusion, the inhibitory effects induced by i.c.v. CCPA or i.t. ZM24138 were significantly greater than those by i.t. or i.c.v. administration, respectively. Intravesical administration of CCPA, but not ZM24138, significantly increased ICI.

Conclusions

These results indicated that: (1) when nociceptive signals from the bladder increase, adenosine A1 receptor-mediated inhibition of micturition is enhanced in the brain, compared to the normal condition, (2) A1 receptor activation also exerts a peripheral inhibitory effect on micturition, and (3) adenosine A2A receptor-mediated excitatory mechanisms are enhanced in the spinal cord following C-fiber bladder afferent stimulation. Thus adenosine A1 receptor agonists and A2A receptor antagonists might be effective for the treatment of overactive bladder and/or bladder hypersensitive disorders, in which C-fiber afferent function is enhanced. Neurourol. Urodynam. 33:1259–1265, 2014. © 2013 Wiley Periodicals, Inc.

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