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

The substance Arg-Pro-Lys-Pro-(CH2)11CH3 [SP1-4C12] was synthesized by forming a peptide bond between Arg-Pro-Lys-Pro, the N-terminal sequence of substance P and dodecylamine. The aim was to examine the roles of the N- and C-terminal sequences of substance P in stimulating histamine release from mast cells of the rat peritoneal cavity. SP1-4 C12 induces concentration-dependent histamine release in the range 8 to 200 nM. SP1-4C12 was 50 times more potent than substance P and 300 times more potent than dodecylamine. Unlike dodecylamine itself, SP1-4C12 induced noncytolytic histamine release which was inhibited by benzalkonium chloride and by the substance P antagonist [D-Pro4,D-Trp7,9,10]SP4-11. Histamine release induced by SP1-4C12 was inhibited at temperatures below 16 degrees C and did not require the presence of extracellular calcium ions. It is suggested that substance P and some other basic histamine liberators initiate histamine secretion by a mechanism that involves the insertion of a hydrophobic region into the membrane lipid which is necessary to present positively charged moieties to a receptor site involved in activating the secretory mechanism.
 ...
PMID:Histamine release induced by Arg-Pro-Lys-Pro(CH2)11CH3 from rat peritoneal mast cells. 244 99

The undecapeptide substance P (SP) contained in primary afferent nerves is thought to mediate that part of the neurogenic inflammatory response consisting of vasodilation and plasma extravasation. This response is diminished in rats pretreated as neonates with the neurotoxin capsaicin. It is not known whether primary afferent nerves influence cellular responses of the immune response to antigenic stimulation. Using 6- to 12-wk-old Sprague-Dawley rats pretreated as neonates with capsaicin, we examined the regional lymph node response to a s.c. antigenic stimulus of sheep red blood cells. The number of cells secreting antigen-specific antibody in these animals was reduced by more than 80% using direct and indirect plaque assay methods. The reduced antibody response in capsaicin-pretreated animals was reversed by a s.c. infusion of SP given over a 4-hr period at the injection site immediately after antigen stimulation. This response had a threshold at approximately 1.0 X 10(-5) M SP. SP1-7 (1.0 X 10(-5) M) was without effect but an infusion of SP5-11 (1.0 X 10(-5) M) reversed the effects of capsaicin treatment indicating a carboxyl-terminal effect of SP. The results suggest that the reduced response of capsaicin-treated animals to an antigenic stimulus is due to an effect of capsaicin on the SP-containing primary afferent nerves rather than a toxic effect of capsaicin on the immune system.
 ...
PMID:The effect of substance P on the regional lymph node antibody response to antigenic stimulation in capsaicin-pretreated rats. 244 15

Biomicroscopic experiments have shown that the N-terminal fragment of substance P (SP1-4), when applied to the rat mesentery, has a considerably lower injuring effect than substance P (SP1-11) itself. SP1-4 activity, as compared to SP1-11 activity regarded as 1, was 0.007 in case of microcirculatory disturbances and venular permeability increase and 0.0007 in case of mast cell degranulation increase. The data obtained suggest that the slightest damaging effect of SP1-4 on microcirculation is combined with anti-stress activity.
 ...
PMID:[Effect of the N-terminal fragment of substance P on the microcirculatory system]. 245 44

A fraction enriched in neuronal growth cones isolated from developing rat forebrain was shown to possess binding sites for the substance P analog, Bolton-Hunter substance P [( 125I]BHSP). Specific binding of this ligand reached an equilibrium after 10 min at 20 degrees C, and was reversible and temperature-dependent. Removal of extracellular Na+ did not block but rather augmented [125I]BHSP binding suggesting that the labeled analog was not transported into the growth cone fraction. Scatchard analysis of the binding indicated a single class of non-interacting binding sites in the growth cone fraction (Kd: 257 pM; Bmax: 56 fmol/mg protein). From competition studies using substance P and other tachykinins, their rank order of potency for inhibiting [125I]BHSP binding was SP greater than physalaemin much greater than eledoisin greater than kassinin greater than NKB greater than or equal to NKA. Such order is consistent with the presence of an SP receptor (Neurokinin-1) in the growth cone fraction. The N-terminal fragments of substance P, SP1-7 and SP1-11 free acids, and the C-terminal fragment, SP7-11, were devoid of affinity for the [125I]BHSP binding site. However SP6-11 and SP1-11 methyl esters showed more potency.
 ...
PMID:An isolated growth cone-enriched fraction from developing rat brain has substance P binding sites. 245 47

1. Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 microM to 30 microM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2. The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle. 3. The relative potencies of substance P and its fragments SP2-11, SP3-11, SP4-11 and SP1-4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4. Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6. The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activation-secretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.
 ...
PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

A reversed-phase high-performance liquid chromatographic procedure combined with radioimmunoassay (HPLC-RIA) was developed and optimized for the concomitant quantitation of substance P (SP) and some of its C- and N-terminal fragments in the extracts of the spinal cord of mice. A selective and efficient solid-phase extraction protocol was used for preparative purification of sample homogenates prior to analyses. The sensitivity of the HPLC assay was 18.75 ng for SP and some of its fragments of interest. Recoveries of peptides were calculated from spiked aqueous standards carried through the experimental protocol and ranged from 53 to 98%. The precision of the peptide recoveries from aqueous-based standards, expressed as coefficient of variation, ranged from 2 to 28%. The sensitivities for the RIA procedure using SP antiserum were 1.5, 3.4 and 4.6 fmol SP1-11, SP2-11 and SP5-11, respectively. The percentage cross-reactivity of SP1-11 antiserum with the C-terminal fragments was complete whereas the cross-reactivities of the N-terminal fragments were essentially zero. The molar limits of detectability of SP and some of its C-terminal fragments determined by HPLC alone were several orders of magnitude greater than those determined from the same spinal cord samples using RIA after HPLC fractionation.
 ...
PMID:Optimization of high-performance liquid chromatography-radioimmunoassay protocols for the analyses of substance P and some of its metabolic fragments. 246 6

The present study was undertaken to study the ability of substance P (SP) to induce inositol phospholipid (IP) hydrolysis measured as inositol mono-phosphate (IP1) accumulation, in an in vivo blister model of neurogenic inflammation in the rat hind footpad. SP was found to induce IP1 accumulation in a concentration dependent manner. The use of SP analogues (SP5-11 and SP1-7) indicated that the response is mainly mediated by the C-terminal sequence of the peptide. The response was significantly reduced by the SP antagonist spantide, suggesting that the response is mostly due to activation of the SP receptor on small diameter vessels. Capsaicin pretreatment did not have an effect on the ability of SP to induce the response. Experiments with mepyramine suggest that the response is also partly mediated by SP induced histamine release from mast cells. This is the first study to provide direct evidence for phosphoinositide mediated SP effects in the skin.
 ...
PMID:Substance P induced hydrolysis of inositol phospholipids in rat skin in an in vivo model of inflammation. 246 33

The biomicroscopy experiments showed that the substance P N-terminal fragment (SP1-4) is not as injurious as the SP1-11 for the rat mesentery. The SP1-4/SP1-11 activity ratio is 0.007 to 1 in case of microcirculation disturbances and venular permeability increase, and 0.0007 to 1 in case of the mast cells degranulation increase. Injection of SP1-11 (125 micrograms/kg) prior to the 5-hr immobilization, enhanced the disturbances in microcirculatory system induced by the stress. Injection of SP1-4 (53 micrograms/kg) led to sedative or narcotic effects in 50% of rats correlated with the normalizing terminal blood flow, venular permeability and mast cells secretory activity.
 ...
PMID:[Effect of substance P and its N-terminal fragment on the components of the normal microcirculatory system and under stress]. 247 68

Using a blister model of inflammation in the rat hind footpad, we have studied the temporal and quantitative contribution of mast cell mediators and prostaglandins to substance P-induced plasma extravasation. In addition substance P-related peptides (neurokinin A, SP5-11 and SP1-7) were tested for their ability to induce a plasma extravasation response and the extent of histamine involvement to the response was determined. The present results show that the plasma extravasation response to substance P consists of an early substance P-mediated response that is independent of other mediators and a late response that involves interaction between substance P, mast cell mediators and prostaglandins. An early histamine-independent response was also mediated by neurokinin A, a tachykinin that shares a common C-terminal with substance P and by a C-terminally directed analogue of substance P, namely SP5-11. On the other hand, a late histamine-dependent response was mediated by the N-terminally directed analogue, SP1-7. The present data are suggestive of a possible sequence of events that might occur during an inflammatory response to substance P and might involve independent actions of its C- and N-terminal.
 ...
PMID:Sequence of events in substance P-mediated plasma extravasation in rat skin. 248 61

The Substance P fragment Arg1-Pro2-Lys3-Pro4 (SP1-4) has been extensively investigated by means of proton nuclear magnetic resonance at 400 MHz. The combined application of different 2D techniques and a comparison of SP1-4 with its derivative SP1-4-amide allowed the complete and unambiguous assignment of the proton NMR spectrum. Conformational data obtained from the different NMR parameters are compared with theoretical calculations. The results suggest that SP1-4 exists, at the chosen experimental conditions, as a stretched molecule.
 ...
PMID:One- and two-dimensional 1H NMR study of the substance P fragment ARG-PRO-Lys-Pro. 248 48


<< Previous 1 2 3 4 5 6 7 Next >>