Dopamine (5.10(-6)-5.10(-4) M) induced a concentration-dependent decrease in short-circuit current (I(sc)) across the rat distal colon. This response was preceded by a transient and inconsistent increase in I(sc). The alpha-adrenoceptor blocker phentolamine and the inhibitors of dopamine-2-like (D(2)-like) receptors L-741,626 and L-745,870 inhibited the dopamine response, suggesting a contribution of adrenergic and dopaminergic receptors. The decrease in I(sc) evoked by dopamine was inhibited by bumetanide, an inhibitor of the basolateral Na(+)-K(+)-2 Cl(-) cotransporter responsible for the uptake of K(+), and by quinine, a blocker of apical K(+) channels, indicating that stimulation of K(+) secretion contributes to the measured change in I(sc). In patch-clamp experiments dopamine hyperpolarized the membrane and increased cellular K(+) current. This response was not concomitant with a change in the intracellular [Ca(2+)] as demonstrated in parallel fura-2 experiments. These results demonstrate that dopamine, like other catecholamines, stimulates colonic K(+) secretion.