Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels

• Published in: Molecular pharmacology Vol. 77; no. 1; pp. 69 - 78
• Main Authors: Tradtrantip, Lukmanee, Namkung, Wan, Verkman, A.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2010; American Society for Pharmacology and Experimental Therapeutics; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: 3-isobutyl-1-methylxanthine; Anoctamin-1; Antidiarrheals - pharmacology; CaCC; calcium-activated chloride channel; Cell Line; CFTR; CFTRinh-172; Chloride Channels - antagonists & inhibitors; chlorophenylthio-cAMP; CPT-cAMP; Croton - chemistry; cystic fibrosis transmembrane conductance regulator; Cystic Fibrosis Transmembrane Conductance Regulator - antagonists & inhibitors; Fisher rat thyroid; FRT; glycine hydrazide cystic fibrosis transmembrane conductance regulator inhibitor; GlyH-101; Humans; IBMX; Inhibitory Concentration 50; Intestinal Mucosa - metabolism; Membrane Proteins - antagonists & inhibitors; Membrane Transport Proteins - drug effects; N-methyl-d-glucamine chloride; Neoplasm Proteins - antagonists & inhibitors; NMDG-Cl; Proanthocyanidins - pharmacology; Proanthocyanidins - therapeutic use; Signal Transduction - drug effects; thiazolidinone cystic fibrosis transmembrane conductance regulator inhibitor; CaCC; GlyH-101; IBMX; CFTRinh-172; CPT-cAMP; FRT; CFTR; NMDG-Cl

Crofelemer, a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri, is in clinical trials for secretory diarrheas of various etiologies. We investigated the antisecretory mechanism of crofelemer by determining its effect on the major apical membrane transport and signa...