Priming effects of substance P on calcium changes evoked by interleukin-8 in human neutrophils.
The neurokinin (NK) substance P (SP), which is a mediator of neurogenic inflammation, has been reported to prime human polymorphonuclear neutrophils (PMNs). The priming effects of SP on PMNs activated by recombinant interleukin-8 (rIL-8) were investigated. SP enhanced, in a dose- and time-dependent way, the rise in cytosolic free-calcium concentration, [Ca(2+)]i, evoked by the chemokine. The priming effects of SP were abolished by exposing PMNs to a calcium-free medium supplemented with EGTA. The C-terminal peptides SP(4-11) and SP(6-11) but not the N-terminal peptide SP(1-7) shared the priming effects of SP. The selective NK-1 receptor agonist [Sar-9, MetO2-11]SP mimicked the effects of SP, which were not reproduced by the selective NK-2 receptor agonist [betaAla-8]-NKA(4-10) or the selective NK-3 agonist senktide. Two selective NK-1 antagonists, CP96,345 and L703,606, dose dependently inhibited SP priming effects. These results demonstrated that SP primes PMNs exposed to rIL-8 and suggested that SP priming effects are receptor mediated.
Dianzani
C
C
Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy.
Lombardi
G
G
Collino
M
M
Ferrara
C
C
Cassone
M C
MC
Fantozzi
R
R
D000328:Adult; D001713:Biphenyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000187:drug effects; D018042:Receptors, Neurokinin-3 / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology*
D001713:Biphenyl Compounds; D015220:Calcium Channels; D016209:Interleukin-8; D010446:Peptide Fragments; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D011994:Recombinant Proteins; C054724:senktide; C062618:substance P, Sar(9)-Met(O2)(11)-; C076851:L 703606; D013373:Substance P; C032292:substance P (6-11); D004533:Egtazic Acid; C032682:substance P (4-11); C036877:substance P (1-7); D002118:Calcium; D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345