1. Rat foetal distal lung epithelial cells were plated onto permeable supports where they became integrated into epithelial sheets that spontaneously generated short circuit current (I(SC))
2. Apical ATP (100 μM) evoked a transient fall in I(SC) that was followed by a rise to a clear peak which, in turn, was succeeded by a slowly developing decline to a value below control. Apical UTP evoked an essentially identical response.
3. UDP and ADP were ineffective whilst ATP had no effect when added to the basolateral solution. These effects thus appear to be mediated by apical P2Y2 receptors.
4. The rising phase of the responses to ATP/UTP was selectively inhibited by anion transport inhibitors but persisted in the presence of amiloride, which abolished the inhibitory effects of both nucleotides. Thus, apical nucleotides appear to evoke a transient stimulation of anion secretion and sustained inhibition of Na+ absorption.
5. Basolateral isoprenaline (10 μM) elicited a rise in I(SC) but subsequent addition of apical ATP reversed this effect. Conversely isoprenaline restored I(SC) to its basal level following stimulation with ATP. Apical P2Y2 receptors and basolateral β-adrenoceptors thus allow their respective agonists to exert mutually opposing effects on I(SC).