Possible mechanisms of the concentration-dependent action of substance P to induce histamine release from rat peritoneal mast cells and the effect of extracellular calcium on mast-cell activation

Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca²⁺ indicator fura-2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations (Ca²⁺]_i) were measured by a spectrofluorometric assay. SP at 5 × 10^?6 mol/1 and 10^?5 mol/1 caused a significant histamine release with a significant increase in Ca²⁺]_i in a dose-dependent manner. However, SP at 10^?8-10^?6 mol/1 did not induce either histamine release or increase in Ca²⁺]_i. Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of Ca²⁺]ⁱ compared with that of the cells in a nominally calcium-free condition. These results indicate that the action of SP on rat mast cells relies upon Ca²⁺]_i to induce histamine release.