Lubiprostone is non-selective activator of cAMP-gated ion channels and Clc-2 has a minor role in its prosecretory effect in intestinal epithelial cells.

ABSTRACT: Loss of prosecretory Cl^- channel CFTR activity is considered as the key cause of gastrointestinal disorders in cystic fibrosis including constipation and meconium ileus. Clc-2 is proposed as an alternative Cl^- channel in intestinal epithelia that can compensate for CFTR loss-of-function. Lubiprostone is an FDA-approved drug with Clc-2 activation as its presumed mechanism of action. However, relative contribution of Clc-2 in intestinal Cl^- secretion and the mechanism of action of lubiprostone remain controversial due to lack of selective Clc-2 inhibitors. Using recently identified selective Clc-2 inhibitor AK-42, we characterized the roles of Clc-2 in Cl^- secretion in human intestinal epithelial T84 cells. Clc-2 inhibitor AK-42 had minimal (15%) i

SUBMITTER: Oak AA 

PROVIDER: S-EPMC9341254 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature