Key role of down-regulated in adenoma (SLC26A3) chloride/bicarbonate exchanger in linaclotide-stimulated intestinal bicarbonate secretion upon loss of CFTR function.

ABSTRACT: Duodenal bicarbonate secretion is critical to epithelial protection, nutrient digestion/absorption and is impaired in cystic fibrosis (CF). We examined if linaclotide, typically used to treat constipation, may also stimulate duodenal bicarbonate secretion. Bicarbonate secretion was measured in vivo and in vitro using mouse and human duodenum (biopsies and enteroids). Ion transporter localization was identified with confocal microscopy and de novo analysis of human duodenal single cell RNA sequencing (sc-RNAseq) datasets was performed. Linaclotide increased bicarbonate secretion in mouse and human duodenum in the absence of CFTR expression (Cftr knockout mice) or function (CFTR_inh-172). NHE3 inhibition contributed to a portion of this response. Linaclotide-stimulated bicar

SUBMITTER: Sarthi JB 

PROVIDER: S-EPMC10187319 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature