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The role of corticotropin releasing factor and its antagonist, astressin, on micturition in the rat

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Author

Summary, in English

The purpose of this investigation was to evaluate the role of corticotropin releasing factor (CRF) on micturition. CRF is involved in the endocrine and central nervous system responses to stress and is also expressed in sites responsible for the control of micturition. In this investigation, cystometric experiments were performed in awake and unrestrained Wistar rats and on Spontaneous Hypertensive Rats, which are used as a rodent model of detrusor overactivity and anxiety. In vitro effects of CRF were evaluated using strips of detrusor muscle in an organ bath preparation. CRF (6.0 mu g) administered via intrathecal and intraperitoneal routes, but not intracerebroventricularly, lowered the micturition threshold. CRF reduced the intercontraction interval by 28% and 26% after intrathecal or intraperitoneal administration, respectively, and reduced micturition volume by 34.7% and 30.2%, respectively. In Wistar-Kyoto rats, 6.0 mu g intrathecal CRF significantly reduced intercontraction interval (423 +/- 79 vs. 669 +/- 59s) and micturition volume (0.30 +/- 0.04 vs. 0.69 +/- 0.07 ml) compared to controls that received saline vehicle. These effects were blocked by pretreatment with 6.0 mu g intrathecal astressin, a potent CRF antagonist, demonstrating that the effects are CRF receptor mediated. In Spontaneous Hypertensive Rats, 6.0 mu G intrathecal CRF was found to have minimal stimulatory effects on the bladder, whereas astressin reduced baseline detrusor overactivity. CRF had no direct contractile effects on detrusor muscle strips. These results demonstrate that in the absence of detrusor overactivity, CRE stimulates micturition when administered via the intrathecal or intraperitoneal routes. Further studies are needed to explore the possibility whether CRF antagonists are effective for detrusor overactivity and the overactive bladder syndrome.

Publishing year

2005

Language

English

Pages

26-35

Publication/Series

Autonomic Neuroscience: Basic & Clinical

Volume

123

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Medicinal Chemistry
  • Pharmacology and Toxicology

Keywords

  • rats
  • urination
  • corticotropin releasing factor
  • bladder
  • spontaneous
  • hypertensive rat

Status

Published

ISBN/ISSN/Other

  • ISSN: 1872-7484