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Effects of leukotriene C4 on the bioelectric properties and ion transport of equine tracheal epithelium

Guy D. Lester BVMS, PhD1 and Brett L. Rice BS2
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  • 1 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 2 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

Abstract

Objective—To determine effects of leukotriene (LT) C4 on ion transport across equine tracheal epithelium.

Sample—Tracheal epithelium from cadavers of 24 horses considered free of respiratory tract disease.

Procedures—Mucosae were mounted into Ussing chambers, and short-circuit current (Isc) was monitored over time. Effects of LTC4 were examined for various conditions, including addition of amiloride (10μM) to the mucosal bath solution, addition of bumetanide (10μM) to the serosal bath solution, addition of barium (1mM) to the serosal bath solution, and substitution of gluconate for chloride and HEPES for bicarbonate in bath solutions. Electrolyte transport was assessed via 22Na and 36Cl isotope fluxes.

Results—Addition of LTC4 (50nM) to the serosal bath solution caused an increase in Isc for basal conditions and a larger increase after pretreatment with amiloride. The increase was negated in part by the addition of bumetanide to the serosal bath solution and further reduced by substitution of HEPES for bicarbonate in bath solutions. Remaining current was reduced to values less than those before treatment with LTC4 by the addition of barium to the serosal solution. There was a small increase in Isc after the addition of amiloride and substitution of gluconate for chloride. Radioisotope flux indicated that addition of LTC4 to the serosal bath solution increased chloride secretion and reduced sodium absorption.

Conclusions and Clinical Relevance—LTC4 stimulated chloride secretion through a predominately bumetanide-sensitive pathway, with a smaller contribution from a bicarbonate-dependent pathway. Thus, LTC4 appears to be a potential mediator of airway hypersecretion in horses.

Abstract

Objective—To determine effects of leukotriene (LT) C4 on ion transport across equine tracheal epithelium.

Sample—Tracheal epithelium from cadavers of 24 horses considered free of respiratory tract disease.

Procedures—Mucosae were mounted into Ussing chambers, and short-circuit current (Isc) was monitored over time. Effects of LTC4 were examined for various conditions, including addition of amiloride (10μM) to the mucosal bath solution, addition of bumetanide (10μM) to the serosal bath solution, addition of barium (1mM) to the serosal bath solution, and substitution of gluconate for chloride and HEPES for bicarbonate in bath solutions. Electrolyte transport was assessed via 22Na and 36Cl isotope fluxes.

Results—Addition of LTC4 (50nM) to the serosal bath solution caused an increase in Isc for basal conditions and a larger increase after pretreatment with amiloride. The increase was negated in part by the addition of bumetanide to the serosal bath solution and further reduced by substitution of HEPES for bicarbonate in bath solutions. Remaining current was reduced to values less than those before treatment with LTC4 by the addition of barium to the serosal solution. There was a small increase in Isc after the addition of amiloride and substitution of gluconate for chloride. Radioisotope flux indicated that addition of LTC4 to the serosal bath solution increased chloride secretion and reduced sodium absorption.

Conclusions and Clinical Relevance—LTC4 stimulated chloride secretion through a predominately bumetanide-sensitive pathway, with a smaller contribution from a bicarbonate-dependent pathway. Thus, LTC4 appears to be a potential mediator of airway hypersecretion in horses.

Contributor Notes

Dr. Lester's present address is School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA 6150, Australia.

Address correspondence to Dr. Lester (G.Lester@murdoch.edu.au).