Differential sensitivity to nickel and SK&F96365 of second messenger-operated and receptor-operated calcium channels in rat submandibular ductal cells

The intracellular concentration of calcium ([Ca2+](i)) of rat submandibular ductal cells was measured with the intracellular fluorescent dye Fura-2. Carbachol (100 mu M) and ATP (1 mM) both increased the [Ca2+](i). The late response to ATP was blocked by 0.5 mM Ni2+. This concentration of Ni2+ also blocked the increase of the [Ca2+](i) and the uptake of manganese and calcium in response to 2'- and 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP, 100 mu M), a specific agonist of P2X receptors from salivary glands. The increase of the [Ca2+](i) in response to 2-methylthioadenosine 5'-triphosphate (2-MeSATP, 100 mu M) a specific P2Y agonist in salivary glands or to a muscarinic agonist (carbachol) was not affected by 0.5 mM Ni2+. Only higher concentrations of Ni2+ tin the millimolar range) inhibited the uptake of extracellular calcium in response to carbachol. SK&F 96365, a blocker of store-operated calcium channels, inhibited the uptake of extracellular calcium in response to carbachol without affecting the response to BzATP. It is concluded that at low concentrations (below 0.5 mM), Ni2+ inhibits the non-specific cation channel coupled to P2X receptors. The uptake of extracellular calcium by store-operated calcium channels is inhibited by higher concentrations of Ni2+ and by SK&F96365.