| First Author | Stephens CE | Year | 2019 |
| Journal | Exp Physiol | Volume | 104 |
| Issue | 3 | Pages | 334-344 |
| PubMed ID | 30615234 | Mgi Jnum | J:277389 |
| Mgi Id | MGI:6330941 | Doi | 10.1113/EP087445 |
| Citation | Stephens CE, et al. (2019) (125) Iodide as a surrogate tracer for epithelial chloride transport by the mouse large intestine in vitro. Exp Physiol 104(3):334-344 |
| abstractText | 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. |
