title: The role of corticotropin releasing factor and its antagonist, astressin, on micturition in the rat.
abstract: 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 microg) 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 microg intrathecal CRF significantly reduced intercontraction interval (423 +/- 79 vs. 669 +/- 59 s) 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 mug intrathecal astressin, a potent CRF antagonist, demonstrating that the effects are CRF receptor mediated. In Spontaneous Hypertensive Rats, 6.0 mug 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, CRF 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.
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, 22908-0422, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Klausner
authors.forename: Tomi
authors.initials: T
authors.lastname: Streng
authors.forename: Yong-Gil
authors.initials: YG
authors.lastname: Na
authors.forename: Jerry
authors.initials: J
authors.lastname: Raju
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Batts
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Tuttle
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: William D
authors.initials: WD
authors.lastname: Steers
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D002404:Catheterization; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology; D014546:Urinary Catheterization; D014554:Urination / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D010446:Peptide Fragments; C104416:astressin; D003346:Corticotropin-Releasing Hormone