Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
Original Basic Science Article
Roles of adenosine A1 and A2A receptors in the control of micturition in rats
Article first published online: 9 SEP 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
How to Cite
Kitta, T., Chancellor, M. B., de Groat, W. C., Kuno, S., Nonomura, K. and Yoshimura, N. (2013), Roles of adenosine A1 and A2A receptors in the control of micturition in rats. Neurourol. Urodyn.. doi: 10.1002/nau.22487
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.
- Article first published online: 9 SEP 2013
- Manuscript Accepted: 29 JUL 2013
- Manuscript Received: 4 MAY 2013
- National Institute of Health. Grant Numbers: P01 DK093424, DK088836
- Department of Defense. Grant Numbers: W81XWH-11-1-0763, W81XWH-12-1-0565
- Japanese Ministry of Health, Labour and Welfare
- adenosine receptors;
- bladder overactivity;
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.
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.
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.
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. © 2013 Wiley Periodicals, Inc.