The intracellular concentration of calcium ([Ca 2+] i) of rat submandibular ductal cells was measured with the intracellular fluorescent dye Fura-2. Carbachol (100 μM) and ATP (1 mM) both increased the [Ca 2+] j. The late response to ATP was blocked by 0.5 mM Ni 2+. This concentration of Ni 2+ also blocked the increase of the [Ca 2+] i and the uptake of manganese and calcium in response to 2′-and 3′-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP, 100 μM), a specific agonist of P2X receptors from salivary glands. The increase of the [Ca 2+] i in response to 2-methylthioadenosine 5′-triphosphate (2-McSATP, 100 μM) a specific P2Y agonist in salivary glands or to a muscarinic agonist (carbachol) was not affected by 0.5 mM Ni 2+. Only higher concentrations of Ni 2+(in the millimolar range) inhibited the uptake of extracellular calcium in response to carbachol. SK&F 96365, a …