Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP4 receptor antagonist on cyclophosphamide-induced overactive bladder in rats.

Abstract

OBJECTIVE:

To investigate the expression of four subtypes of E-series prostaglandin (EP(1) -EP(4) ) receptors and the urodynamic effects of an EP(4) receptor antagonist (AH23848) in cyclophosphamide (CYP)-induced overactive bladder (OAB) in rats, as intravesical prostaglandin E(2) (PGE(2) ) induces OAB via activation of EP receptors and sensitization of afferent nerves.

MATERIALS AND METHODS:

Experimental and control rats were injected with CYP (200 mg/kg, intraperitoneally) or saline, respectively. Continuous cystometrograms (CMGs) were performed 48 h after CYP or saline injection under urethane anaesthesia. AH23848 was given intravenously at doses of 0.01 and 0.1 mg/kg. The bladder was then harvested for histology. Some bladders were harvested for analysis of EP receptors expression by Western blotting without a CMG study. CMG variables (baseline pressure; intercontraction interval [ICI], pressure threshold [PT], contraction amplitude) and histological changes were measured.

RESULTS:

CYP-induced up-regulation of EP(4) receptor (100% increase) accompanied by detrusor overactivity (ICI 70.5% decrease; PT, 67.7% increase). However, CYP down-regulated EP(1) receptor expression (51.9% decrease), but had no significant effects on the EP(2) and EP(3) receptors. AH23848 significantly extended the ICI in CYP-treated rats but it had no effects on other urodynamic variables or in control rats.

CONCLUSIONS:

Modulation of EP receptors plays a role in CYP-induced OAB. Antagonists to the EP(4) receptor may be a new target for treatment of patients with OAB.

• Authors: Yao-Chi Chuang, Naoki Yoshimura, Chao-Cheng Huang, Moya Wu, Pradeep Tyagi, Michael B Chancellor
• Journal: BJU international (BJU Int) Vol. 106 Issue 11 Pg. 1782-7 (Dec 2010) ISSN: 1464-410X [Electronic] England
• PMID: 20346049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

Chemical References

• Biphenyl Compounds
• Receptors, Prostaglandin E
• Receptors, Prostaglandin E, EP4 Subtype
• AH 23848
• Cyclophosphamide

Topics

• Animals
• Biphenyl Compounds (pharmacology)
• Blotting, Western
• Cyclophosphamide
• Female
• Immunohistochemistry
• Photomicrography
• Rats
• Rats, Sprague-Dawley
• Receptors, Prostaglandin E (antagonists & inhibitors, metabolism)
• Receptors, Prostaglandin E, EP4 Subtype (antagonists & inhibitors)
• Up-Regulation
• Urinary Bladder, Overactive (drug therapy, pathology)
• Urodynamics (drug effects)