Endoscopy 2006; 38 - Oral_23
DOI: 10.1055/s-2006-956885

The Efficacy of Novel CFTR Inhibitors on the Secretory Funtion of Human Colonic Mucosa

A Patel 1, DI Bovell 2, AD Corbett 2, RJ Holdsworth 1
  • 1Department of Surgery, Stirling Royal Infirmary, Stirling
  • 2Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow

Category: Colorectal

Aims: To examine the efficacy of the novel Cystic Fibrosis Transmembrane Regulator (CFTR) inhibitors CFTR inh-172 and GlyH-101 on secretory responses to carbachol in human colonic mucosa.

Methods: Human colonic mucosa was mounted in Ussing chambers permitting the measurement of changes in short circuit currents (DIsc). CFTR inh-172 (5 mM) and GlyH-101 (10 mM, 30mM and 100mM) were added apically 30min prior to stimulating with carbachol (a stable acetylcholine analogue). The DIsc was measured following addition of the drug and following carbachol stimulation.

Results: Carbachol caused a rise in Isc of 134±42.2 mAcm-2 representing a secretory response. The DIsc caused by carbachol was not decreased by either CFTR inh-172 (n=3) or GlyH-101 (n=5). Neither inhibitor affected the resting Isc.

Conclusions: Both CFTR inh-172 and GlyH-101 have been shown to be effective CFTR inhibitors in rat colonic mucosa. However, neither drug appears to be effective in human colonic mucosa.