Drug-induced secretory diarrhea: A role for CFTR.

Abstract

Many medications induce diarrhea as a side effect, which can be a major obstacle to therapeutic efficacy and also a life-threatening condition. Secretory diarrhea can be caused by excessive fluid secretion in the intestine under pathological conditions. The cAMP/cGMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR) is the primary chloride channel at the apical membrane of intestinal epithelial cells and plays a major role in intestinal fluid secretion and homeostasis. CFTR forms macromolecular complexes at discreet microdomains at the plasma membrane, and its chloride channel function is regulated spatiotemporally through protein-protein interactions and cAMP/cGMP-mediated signaling. Drugs that perturb CFTR-containing macromolecular complexes in the intestinal epithelium and upregulate intracellular cAMP and/or cGMP levels can hyperactivate the CFTR channel, causing excessive fluid secretion and secretory diarrhea. Inhibition of CFTR chloride-channel activity may represent a novel approach to the management of drug-induced secretory diarrhea.

• Authors: Changsuk Moon, Weiqiang Zhang, Nambirajan Sundaram, Sunitha Yarlagadda, Vadde Sudhakar Reddy, Kavisha Arora, Michael A Helmrath, Anjaparavanda P Naren
• Journal: Pharmacological research (Pharmacol Res) Vol. 102 Pg. 107-112 (Dec 2015) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 26429773 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Cystic Fibrosis Transmembrane Conductance Regulator
• Cyclic AMP
• Cyclic GMP

Topics

• Animals
• Cell Membrane (drug effects, metabolism)
• Cyclic AMP (metabolism)
• Cyclic GMP (metabolism)
• Cystic Fibrosis Transmembrane Conductance Regulator (metabolism)
• Diarrhea (chemically induced, metabolism)
• Drug-Related Side Effects and Adverse Reactions (metabolism)
• Humans