Luminal oxidants selectively modulate electrogenic ion transport in rat colon

Abstract

To investigate the effects of luminal exposure to H2O(2) and two related thiol oxidizing agents on basal and stimulated chloride secretion in native colon using electrophysiological and pharmacological approaches. Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, calculated resistance and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. Paracellular permeability was assessed by measuring the mucosa-to-serosa flux of a fluorescent probe (FITC). Luminal exposure to hydrogen peroxide transitorily stimulated chloride secretion without altering barrier function. This stimulatory effect could be blocked by basolateral atropine but not indomethacin. The cysteine and methionine oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked the effect of H2O(2), except for a drop in transcolonic resistance after 30 min. In contrast to the observed stimulatory effect on basal secretion, cAMP-stimulated electrogenic ion transport was blunted by luminal H2O(2). However, the Ca(2+)-activated response remained unchanged. H2O(2) may be an important selective modulator of intestinal ion and water secretion in certain pathologic conditions such as inflammation or ischemia-reperfusion by multiple mechanisms.