EBIO, an agent causing maintained epithelial chloride secretion by co-ordinate actions at both apical and basolateral membranes

The effect of 1-ethyl-2-benzimidazolone (EBIO) on electrogenic chloride sec retion in murine colonic and nasal epithelium was investigated by the short -circuit technique. In the colon, EBIO produces a sustained current increas e in the presence of amiloride, which is sensitive to furosemide. In nasal epithelium EBIO causes only a small, transient current increase. Sustained increases in current were obtained in response to forskolin in both epithel ia. To examine the mechanisms by which EBIO increases chloride secretion, t he effects on intracellular mediators were measured in colonic crypts. Ther e was no effect on [Ca2+](i) but cAMP content was increased, more so in the presence of IBMX, indicating a direct effect on adenylate cyclase. In colo nic epithelia in which the apical surface was permeabilized by nystatin, an d the tissue subjected to an apical to basolateral K+ gradient, EBIO caused a current increase that was entirely sensitive to charybdotoxin (ChTX). In similarly permeabilized colons Br-cAMP caused a current increase that was entirely sensitive to 293B. Thus EBIO increases chloride secretion in the c olon by coordinated actions at both the apical and basolateral faces of the cells. These include direct and indirect actions on Ca2+-sensitive and cAM P-sensitive K+ channels respectively, and indirect actions on the basolater al cotransporter and apical CFTR chloride channels via cAMP. In CF colonic epithelia EBIO did not evoke chloride secretion. It is not clear why the na sal epithelium responds poorly to EBIO whereas it gives a sustained respons e to the related compound chlorzoxazone.