Recent evidence indicates that binding of extracellular nucleotides such as ATP to purinergic receptors can modify many cellular responses including ion transport. We have recently identified ATP-activated purinergic (P2) receptors on the luminal membrane of principal cells in the rabbit CCD (J Am Soc Neph 7:1681A, 1996); these cells are responsible for the final regulation of urinary K+ secretion. To determine whether K+ secretion in the CCD is regulated by the purinergic system, we examined the effects of the P2 purinergic receptor antagonist suramin (100 μM) and the ATP scavenger apyrase (1 u/ml) on net K+ transport in isolated microperfused rabbit CCDs. We found that luminal application of suramin led to inhibition of net K+ secretion (-5.6 ± 1.0 to -2.5 ± 0.4 pmol/min.mm; n=5; p<0.05), as did luminal perfusion with apyrase (-12.5± 2.7 to -6.5 ± 2.6 pmol/min.mm; n=3; p=0.05). These data suggest that activation of apical P2 purinergic receptors by ATP or other nucleotides secreted locally into the lumen of the CCD may regulate K+ transport.