Iodide as a surrogate tracer for epithelial chloride transport by the mouse large intestine in vitro.

Author(s) Stephens, C.E.; Whittamore, J.M.; Hatch, M.
Journal Exp Physiol
Date Published 2019 Jan 07

NEW FINDINGS: What is the central question of this study? The tracer Chloride ( Cl ), currently used to measure transepithelial Cl fluxes, has become prohibitively expensive threatening its future use. Iodide, previously validated alongside Cl as a tracer of Cl efflux by cells, has not been tested as a surrogate for Cl across epithelia. What is the main finding and its importance? We demonstrate that Iodide can serve as an inexpensive replacement for measuring Cl transport across mouse large intestine, tracking Cl transport in response to cAMP stimulation (inducing Cl secretion) in the presence and absence of the main gastrointestinal Cl /HCO exchanger, DRA.

ABSTRACT: Chloride (Cl ) transport is important for driving fluid secretion and absorption by the large intestine with dysregulation resulting in diarrhea-associated pathologies. The radioisotope Cl has long been used as a tracer to measure epithelial Cl transport but is prohibitively expensive. Iodide has been used as an alternative to Cl in some transport assays but has never before been validated as an alternative for tracing bidirectional transepithelial Cl fluxes. This study's goal was to validate I as an alternative to Cl for measuring Cl transport by the intestine. Simultaneous fluxes of Cl and I were measured across the mouse cecum and distal colon. Net Cl secretion was induced by the stimulation of cAMP with a cocktail of forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX). Unidirectional fluxes of I correlated well with Cl fluxes following cAMP-induced net Cl secretion, occurring predominantly through a reduction in the absorptive mucosal-to-serosal Cl flux rather than stimulation of the secretory serosal-to-mucosal Cl flux. Correlations between I fluxes and Cl fluxes were maintained in epithelia from mice lacking DRA (Slc26a3), the main Cl /HCO exchanger responsible for Cl absorption by the large intestine. Lower rates of Cl and I absorption in the DRA KO intestine suggest that DRA may have a previously unrecognized role in iodide I uptake. This novel study validates I traces transepithelial Cl fluxes across the mouse large intestine, provides insights into the mechanism of net Cl secretion and suggests DRA may be involved in intestinal iodide absorption. This article is protected by copyright. All rights reserved.

DOI 10.1113/EP087445
ISSN 1469-445X
Citation Exp Physiol. 2019.

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