The flavonol naringenin stimulates Cl‐ secretion in rat distal colon and T84 cells via CFTR

Abstract

The aim of this study was to investigate the effect of naringenin (NAR) on the rat colon mucosa and in T84 cells. Mucosal addition of NAR (10μM-1mM) elicited a concentration dependent, and sustained increase in short-circuit current (Isc). The increase in Isc was inhibited when the mucosa was bathed in Cl- free KH solution or by inhibiting basolateral chloride uptake with bumetanide and apical Cl− exit with DPC, but it wasn’t inhibited by DIDS. Pretreatment of the colonic strips with MDL-12330A caused a significant reduction of NAR-induced Isc, suggesting that the Cl− secretion was via a cAMP-dependent pathway. In addition, this Cl− secretion was significantly inhibited by two K+ channels blockers, namely quinidine and Ba2+, suggesting that basolateral K+ channels are important in the cAMP-dependent Cl− secretion induced by NAR in rat colons. NAR treatment also resulted in increased cAMP content in rat colon. Under whole cell patch-clamp condition, T84 cells responded to NAR with a rise in inward current. The current was inhibited by DPC in a voltage-dependent manner and the reverse potential was close to the equilibrium potential for Cl− (0 mV), suggesting that the current was Cl− selective. Taken together, our data suggest that NAR stimulated Cl− secretion in rat distal colon and human colonic T84 cells via increase in cellular cAMP resulting in the open of apical CFTR.