Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Biphenyl Compounds / pharmacology
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Calcium / metabolism
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Calcium Channels / metabolism
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Calcium Signaling / drug effects*
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Dose-Response Relationship, Drug
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Drug Synergism
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Egtazic Acid / pharmacology
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Humans
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Interleukin-8 / pharmacology*
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Ion Transport / drug effects
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Neutrophils / drug effects*
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Neutrophils / metabolism
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Peptide Fragments / pharmacology
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Pyrrolidonecarboxylic Acid / analogs & derivatives
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Quinuclidines / pharmacology
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Receptors, Neurokinin-1 / drug effects
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Receptors, Neurokinin-2 / drug effects
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Receptors, Neurokinin-3 / drug effects
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Recombinant Proteins / pharmacology
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Substance P / analogs & derivatives*
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Substance P / pharmacology*
Substances
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Biphenyl Compounds
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Calcium Channels
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Interleukin-8
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Peptide Fragments
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Quinuclidines
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Receptors, Neurokinin-1
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Receptors, Neurokinin-2
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Receptors, Neurokinin-3
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Recombinant Proteins
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senktide
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substance P, Sar(9)-Met(O2)(11)-
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L 703606
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Substance P
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substance P (6-11)
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Egtazic Acid
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substance P (4-11)
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substance P (1-7)
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Calcium
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Pyrrolidonecarboxylic Acid
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CP 96345