Relatively little is known about purinergic receptors in HCO₃^- transporting epithelia, such as pancreatic ducts. The aim of our study was to test the effects of various nudeotides on intracellular Ca²⁺ activity, [Ca²⁺h, and on membrane voltage, V_m, of duct cells obtained from rat pancreas. [Ca²⁺]_i was measured using the fura-2 method and V_m was measured with the whole-cell nystatin patch clamp technique. ATP (10^-4 mol/I) evoked a characteristic biphasic Ca²⁺-transient in duct cells. Nucleotides, used to classify the P₂ receptors, acted with the following potency on the peak Ca²⁺: UTP ≈ ATP > ITP ≥ 2-methylthio-ATP > β,γ-methylene-ATP. However, although the peak [Ca²⁺]_i responses to ATP and UTP were similar, the plateau (Ca²⁺]_i was nearly doubled with UTP. Moreover, patch-clamp experiments indicate that ATP depolarized V_m by about 10 mV, but UTP only 2 to 4 mV. In further experiments we found that removal of extracellular Mg²⁺ increased peak (Ca²⁺); response to ATP. Benzoyl-ATP evoked monophasic increase in [Ca²⁺]_i, which was inhibited by removal of extracellular Ca²⁺, or by addition of DIDS. Taken together, our data indicate that there are two types of purinergic receptors on pancreatic ducts through which ATP can act. These are pharmacologically known as P_2U and P_2Z, and may correspond to P_2Y2 and P_2X7, identified by molecular biology.