Whole-cell recordings of an M-type potassium current (IM) were made from dissociated bullfrog sympathetic neurons. Purinoceptor agonists inhibited IM with UTP>ADP>adenosine triphosphate=UDP>ATPγS=guanosine triphosphate (GTP)≫amyloid precursor protein (APP)(NH)P as the rank order of potency. The IC50 was 35 nM for UTP, and 2.6 μM for GTP. Under conditions in which IM was abolished by UTP (1 μM), a sulfonic acid derivative, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) (30–300 μM) recruited IM to 15 to 90% of its control in a reversible and concentration-dependent manner. These results indicate that PPADS can be useful as an antagonist for the purinoceptors presumably P2Y subtypes in amphibian autonomic neurons. [Copyright &y& Elsevier]