The effect of epinephrine on transport of K+, Na+, Cl-, and HCO-3 across the rat colon was studied using the Ussing chamber technique. Epinephrine (5 x 10(-6) mol/l) induced a biphasic change in short-circuit current (Isc) in distal and proximal colon: a transient increase followed by a long-lasting decay. The first phase of the Isc response was abolished in Cl--poor solution or after bumetanide administration, indicating a transient induction of Cl- secretion. The second phase of the response to epinephrine was suppressed by apical administration of the K+ channel blocker, quinine, and was concomitant with an increase in serosal-to-mucosal Rb+ flux, indicating that epinephrine induced K+ secretion, although this response was much smaller than the change in Isc. In addition, the distal colon displayed a decrease in mucosal-to-serosal and serosal-to-mucosal Cl- fluxes when treated with epinephrine. In the distal colon, indomethacin abolished the first phase of the epinephrine effect, whereas the second phase was suppressed by TTX. In the proximal colon, indomethacin and TTX were ineffective. The neuronally mediated response to epinephrine in the distal colon was suppressed by the nonselective beta-receptor blocker, propranolol, and by the beta2-selective blocker, ICI-118551, whereas the epithelial response in the proximal colon was suppressed by the nonselective alpha-blocker, phentolamine, and by the selective alpha2-blocker, yohimbine. These results indicate a segment-specific action of epinephrine on ion transport: a direct stimulatory action on epithelial alpha2-receptors in the proximal colon and an indirect action on secretomotoneurons via beta2-receptors in the distal colon.