¹²⁵ Iodide as a surrogate tracer for epithelial chloride transport by the mouse large intestine in vitro.

NEW FINDINGS:What is the central question of this study? The tracer ³⁶ Cl^- , currently used to measure transepithelial Cl^- fluxes, has become prohibitively expensive, threatening its future use. ¹²⁵ Iodide, previously validated alongside ³⁶ Cl^- as a tracer of Cl^- efflux by cells, has not been tested as a surrogate for ³⁶ Cl^- across epithelia. What is the main finding and its importance? We demonstrate that ¹²⁵ I^- 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^- -HCO₃^- exchanger, DRA. ABSTRACT:Chloride transport is important for driving fluid secretion and absorption by the large intestine, with dysregulation resulting in diarrhoea-associated pathologies. The radioisotope ³⁶ Cl^- has long been used as a tracer to measure epithelial Cl^- transport but is prohibitively expensive. ¹²⁵ Iodide has been used as an alternative to ³⁶ Cl^- in some transport assays but has never been validated as an alternative for tracing bidirectional transepithelial Cl^- fluxes. The goal of this study was to validate ¹²⁵ I^- as an alternative to ³⁶ Cl^- for measurement of Cl^- transport by the intestine. Simultaneous fluxes of ³⁶ Cl^- and ¹²⁵ I^- were measured across the mouse caecum 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 ¹²⁵ I^- correlated well with ³⁶ Cl^- fluxes after cAMP-induced net Cl^- secretion, occurring predominantly through a reduction in the absorptive mucosal-to-serosal Cl^- flux rather than by stimulation of the secretory serosal-to-mucosal Cl^- flux. Correlations between ¹²⁵ I^- fluxes and ³⁶ Cl^- fluxes were maintained in epithelia from mice lacking DRA (Slc26a3), the main Cl^- -HCO₃^- exchanger responsible for Cl^- absorption by the large intestine. Lower rates of Cl^- and I^- absorption in the DRA knockout intestine suggest that DRA might have a previously unrecognized role in iodide uptake. This study validates that ¹²⁵ I^- traces transepithelial Cl^- fluxes across the mouse large intestine, provides insights into the mechanism of net Cl^- secretion and suggests that DRA might be involved in intestinal iodide absorption.

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