The pH dependence of the facilitation by dopamine (10 microM), 5-hydroxytryptamine (10 microM), adenosine (1 and 100 microM), Zn2+ (10 microM) and Cd2+ (1 mM) of P2X2 purinoceptor/channels was tested by expressing these channels in Xenopus oocytes. In a pH range between 6.0 and 8.5, concentration-response curves for an inward current activated by ATP were shifted toward a lower concentration range at a more acidic pH, indicating that the sensitivity to ATP is pH-dependent. Comparison of the effects of the neurotransmitters and the divalent cations on the ATP-activated current was made using a concentration of ATP which activated 40-50% of the maximal current at each pH value. The current facilitation by dopamine was obvious at pH 7.1 and 7.7, but was not observed at pH 8.5. At pH 6.0, the current was inhibited upon first trials of dopamine, but it was facilitated upon second trials. With 5-hydroxytryptamine and adenosine, the current facilitation was most remarkable at pH 6.0, less remarkable at pH 7.1 and 7.7, and the facilitation was almost abolished at pH 8.5. On the other hand, the current facilitation by Zn2+ and Cd2+ was more remarkable at alkaline pH values (7.7 and 8.5), and the facilitation was almost abolished at pH 6.0. The results suggest that the facilitation of P2X2 purinoceptors depends on pH, and the pH dependence was different between the neurotransmitters and the divalent cations.