D Collins1, A M Hogan, M M Skelly, A W Baird, D C Winter. 1. College of Life Sciences & Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Belfield. daniellecol@gmail.com
Abstract
BACKGROUND AND PURPOSE: Prostaglandin F(2alpha) (PGF(2alpha)) is implicated in the pathogenesis of inflammatory bowel disease and colorectal cancer. This study investigates the effects of PGF(2alpha) on electrophysiological parameters in isolated human colonic mucosa. EXPERIMENTAL APPROACH: Ion transport was measured as changes in short-circuit current across human colonic epithelia mounted in Ussing chambers. Colonic crypts were isolated by calcium chelation and cyclic adenosine monophosphate (cAMP) was measured by ELISA. KEY RESULTS: PGF(2alpha) stimulated chloride secretion in a concentration-dependent manner with an EC(50) of 130 nM. The PGF(2alpha) induced increase in chloride secretion was inhibited by AL8810 (10 microM), a specific PGF(2alpha) receptor antagonist. In addition, PGF(2alpha) (1 microM) significantly increased levels of cAMP in isolated colonic crypts. CONCLUSIONS AND IMPLICATIONS: PGF(2alpha) stimulated chloride secretion in samples of human colon in vitro through a previously unrecognizd cAMP-mediated mechanism. These findings have implications for inflammatory states.
BACKGROUND AND PURPOSE:Prostaglandin F(2alpha) (PGF(2alpha)) is implicated in the pathogenesis of inflammatory bowel disease and colorectal cancer. This study investigates the effects of PGF(2alpha) on electrophysiological parameters in isolated humancolonic mucosa. EXPERIMENTAL APPROACH: Ion transport was measured as changes in short-circuit current across humancolonic epithelia mounted in Ussing chambers. Colonic crypts were isolated by calcium chelation and cyclic adenosine monophosphate (cAMP) was measured by ELISA. KEY RESULTS:PGF(2alpha) stimulated chloride secretion in a concentration-dependent manner with an EC(50) of 130 nM. The PGF(2alpha) induced increase in chloride secretion was inhibited by AL8810 (10 microM), a specific PGF(2alpha) receptor antagonist. In addition, PGF(2alpha) (1 microM) significantly increased levels of cAMP in isolated colonic crypts. CONCLUSIONS AND IMPLICATIONS: PGF(2alpha) stimulated chloride secretion in samples of human colon in vitro through a previously unrecognizd cAMP-mediated mechanism. These findings have implications for inflammatory states.
Authors: Y Sugimoto; K Hasumoto; T Namba; A Irie; M Katsuyama; M Negishi; A Kakizuka; S Narumiya; A Ichikawa Journal: J Biol Chem Date: 1994-01-14 Impact factor: 5.157
Authors: Amnah Yamani; David Wu; Richard Ahrens; Lisa Waggoner; Taeko K Noah; Vicky Garcia-Hernandez; Catherine Ptaschinski; Charles A Parkos; Nicholas W Lukacs; Asma Nusrat; Simon P Hogan Journal: Mucosal Immunol Date: 2020-06-23 Impact factor: 7.313
Authors: David C Montrose; Masako Nakanishi; Robert C Murphy; Simona Zarini; Jeremy P McAleer; Anthony T Vella; Daniel W Rosenberg Journal: Prostaglandins Other Lipid Mediat Date: 2014-10-22 Impact factor: 3.072
Authors: Alicia M Hidalgo-Estévez; Konstantinos Stamatakis; Marta Jiménez-Martínez; Ricardo López-Pérez; Manuel Fresno Journal: Front Pharmacol Date: 2020-04-29 Impact factor: 5.810