Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the activity of the four principal cationic proteins of the eosinophil granules, major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin, and eosinophil cationic protein on histamine release from human skin mast cells. These four cationic proteins, over the concentration range of 10 to 200 micrograms/ml, did not induce significant histamine release, nor did they prime anti-IgE-induced histamine release from human skin mast cells significantly. However, a brief incubation (15 minutes) of two of the four principal eosinophil granule proteins, MBP and EPO, at concentrations of 50 to 200 micrograms/ml, caused a significant concentration-related inhibition of histamine release induced by 30 mumol/L substance P. The concentrations producing 50% inhibition for MBP and EPO on substance P-induced histamine release were 30 micrograms/ml and 100 micrograms/ml, respectively. This inhibitory effect appears to be a direct effect of these proteins on skin mast cells because purified (78% to 85%) skin mast cells displayed a similar response to MBP and EPO (n = 4). Also, when skin mast cells were incubated with 100 micrograms/ml MBP and EPO for 15 minutes and washed twice before activation by substance P, the inhibitory effect was not altered. These two proteins also inhibited histamine release induced by 10 micrograms/ml compound 48/80. These results suggest that MBP and EPO affect the same binding site(s) on skin mast cells as those of substance.
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PMID:Eosinophil granule proteins inhibit substance P-induced histamine release from human skin mast cells. 751 97

This study was performed to test the hypothesis that activated eosinophils or their secretory products can directly stimulate sensory neurons to release their neuropeptides. Neurons derived from neonatal rat dorsal root ganglia (DRG), which synthesize and store sensory neuropeptides, were placed in primary cell culture and were exposed to eosinophils or their bioactive mediators. The resultant release of substance P (SP) was measured by enzyme-linked immunosorbent assay and was expressed as a percent (mean +/- SE) of total neuronal SP content. Eosinophils were isolated from human volunteers with a history of allergic rhinitis and/or mild asthma and were activated by incubation with cytochalasin B (5 micrograms/ml) and N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM). Activated eosinophils [6 x 10(6)/ml, suspended in Hanks' buffered salt solution (HBSS)] applied to cultured DRG neurons for 30 min increased basal SP release 2.4-fold compared with HBSS-exposed neurons (activated eosinophils 11.10 +/- 2.48% vs. HBSS 4.59 +/- 0.99%; P = 0.002), whereas neither nonactivated eosinophils nor cytochalasin B and FMLP in HBSS influenced SP release. Additional cultured DRG neurons were exposed to soluble products made by eosinophils. Compared with SP release under control conditions (2.37 +/- 0.34%), major basic protein (MBP) increased release in a concentration-related fashion (e.g., 3 microM MBP: 6.23 +/- 0.67%, P = 0.006 vs. control), whereas neither eosinophil cationic protein (3 microM), eosinophil-derived neurotoxin (3 microM), leukotriene D4 (500 nM), platelet-activating factor (100 nM), nor H2O2 (100 microM) affected SP release. These studies demonstrate that activated eosinophils can stimulate cultured DRG neurons directly and suggest that MBP may be the responsible mediator.
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PMID:Activated eosinophils elicit substance P release from cultured dorsal root ganglion neurons. 937 40

Substance P (SP), a tachykinin with a wide range of biological activities including a priming effect on human eosinophil chemotaxis, was investigated for its influence on eosinophil cytotoxic function measured as degranulation of eosinophil-derived neurotoxin (EDN). Peripheral blood was obtained from healthy volunteers and the degranulation assays were performed using radioimmunoassay (RIA). SP and its C-terminal elicited EDN release in a time-dependent mode at a narrow range of doses with optimal activity of 10(-6) M. FK888 (NK-1 receptor antagonist) inhibited EDN release stimulated by SP in dose dependency, also a complete inhibition was observed when eosinophils were preincubated with 1000 ng/ml pertussis toxin (PTX). Pre-exposure of eosinophils to staurosporine resulted in blockage of SP-induced EDN release in a dose-dependent mode. On the other hand, SP at 10(-7) M and 10(-8) M primed eosinophils to suboptimal dose (10(-8) M) of Platelet activating factor (PAF) resulting into significant enhancement of EDN release. SP(4-11) fragment showed a similar activity while SP(1-4) fragment was not active. SP priming of eosinophils was not affected by Ca2+ depletion, however, it caused a change in the pattern of the intracellular calcium influx against the suboptimal dose of PAF. These results suggest that SP i) may induced human eosinophil matrix protein degranulation through a receptor mediated mechanism coupled to PTX sensitive G protein(s) with the probability of linkage to phospholipase C activation, and, ii) primes human eosinophils for an exalted inflammatory response through a Ca2+ independent pathway.
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PMID:Mechanisms involved in activation of human eosinophil exocytosis by substance P: an in vitro model of sensory neuroimmunomodulation. 939 4