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.
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
I
I
Iwamoto
H
H
Yamazaki
N
N
Nakagawa
A
A
Kimura
H
H
Tomioka
S
S
Yoshida
D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013373:Substance P / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D010446:Peptide Fragments; D013481:Superoxides; D013373:Substance P; C032292:substance P (6-11); C032682:substance P (4-11); D002118:Calcium; D011761:Pyrrolidonecarboxylic Acid