| Loss of muscarinic and purinergic receptors in urinary bladder of rats with hydrochloric acid-induced cystitis. | |
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MedLine Citation:
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PMID: 20719367 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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OBJECTIVES: To clarify the basic mechanism involved in the pathophysiology of cystitis by characterizing the urodynamic parameters, pharmacologically relevant (muscarinic and purinergic) receptors, and the in vivo release of adenosine triphosphate (ATP) in the bladder of hydrochloric acid (HCl)-treated rats. METHODS: The muscarinic and purinergic receptors in rat tissue were measured by radioreceptor assays using (N-methyl-³H) scopolamine methyl chloride ([³H]NMS) and αβ-methylene-ATP (2,8-³H) tetrasodium salt ([³H]αβ-MeATP), respectively. The urodynamic parameters and ATP levels were measured using a cystometric method and the luciferin-luciferase assay, respectively. RESULTS: In the HCl-treated rats, the micturition interval and micturition volume were significantly (48% and 55%, respectively, P <.05) decreased and the number of micturitions was significantly (3.2-fold, P <.05) increased compared with those of the control rats. The maximal number of binding sites for [³H]NMS and [³H]αβ-MeATP was significantly (55% and 72%, respectively, P <.001) decreased in the bladder of HCl-treated rats, suggesting downregulation of both muscarinic and purinergic receptors. In the HCl-treated rats, the inhibition constant, K(i), values for oxybutynin, solifenacin, and darifenacin were significantly (1.3-1.4-fold, P <.05) increased, but those for tolterodine and AF-DX116 were unchanged. Similarly, the inhibition constant for A-317491, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium, and MRS2273 was significantly (5.5, 11, and 7.6-fold, respectively, P <.001) increased. Furthermore, the in vivo release of ATP was significantly (P <.05) enhanced in the HCl-treated rat bladder. CONCLUSIONS: Both muscarinic and purinergic mechanisms might be, at least in part, associated with the urinary dysfunction due to cystitis. |
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Authors:
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Akira Yoshida; Aiko Kageyama; Tomomi Fujino; Yoshihisa Nozawa; Shizuo Yamada |
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Publication Detail:
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Type: Journal Article Date: 2010-08-16 |
Journal Detail:
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Title: Urology Volume: 76 ISSN: 1527-9995 ISO Abbreviation: Urology Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0366151 Medline TA: Urology Country: United States |
Other Details:
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Languages: eng Pagination: 1017.e7-12 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence Program, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan. yamada@u-shizuoka-ken.ac.jp |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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