Differential effects of two C-terminal peptides of substance P on human neutrophils

To determine the mechanism by which substance P (SP) activates human neutrophils, we examined the potencies of SP, the C-terminal peptides SP4–11 and SP6–11, and the N-terminal peptides SP1–9 and SP1–4 for inducing the increase in cytosolic free Ca2+ concentration ([Ca2+]i), superoxide (O2−) generation, and chemotaxis in human blood neutrophils. SP and the C-terminal peptides SP4–11 and SP6–11 and SP6–11 (10−6–10−4M) induced the increase in [Ca2+]i, O2- generation, and chemotaxis of the neutrophils dose-dependently, whereas the N-terminal peptides SP1–9 and SP1–4 (up to 10−4M) were inactive in inducing these responses. Furthermore, the potencies of the two C-terminal peptides SP4–11 and SP6–11 were not parallel in these three responses. SP6–11 was 7.7-fold more potent in increasing [Ca2+]i than SP4–11, whereas SP4–11 was 16.6-fold more potent in inducing O2- generation than SP6–11. SP6–11 was also 2.1-fold more potent in inducing chemotaxis than SP4–11. Thus, we conclude that the C-terminal peptides of SP induce differential activations of human neutrophils.