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(-4) M) 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(-4) M) 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.