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)

Previous studies have shown that substance P induces granulocyte infiltration in mouse skin, which is mediated through mast cell degranulation. However, it is not yet known whether the direct effect of substance P on vascular endothelial cells is involved in the granulocyte infiltration in the skin. To solve this issue, we used the N-terminal peptide substance P1-9 (SP1-9), which is active for mast cells but inactive for vascular endothelial cells, and the C-terminal peptide SP6-11, which is active for vascular endothelial cells but inactive for mast cells, since substance P activates both mast cells and vascular endothelial cells. The subcutaneous administration of substance P (10(-7)-10(-5)M) caused granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice 6 h after the injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration of mouse skin which was associated with mast cell degranulation. In contrast, SP6-11 (10(-7)-10(-4) M), which was found to increase the vascular permeability of endothelial cells in mouse skin, induced no significant granulocyte infiltration nor mast cell degranulation. However, SP6-11 (10(-5)-10(-4) M) enhanced SP1-9-induced granulocyte infiltration in the skin without any significant increase in mast cell degranulation. We conclude that substance P causes granulocyte infiltration in mouse skin through both mast cell degranulation induced by the N-terminal peptide of substance P and the activation of vascular endothelial cells induced by the C-terminal peptide of substance P.
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PMID:Substance P-induced granulocyte infiltration in mouse skin: the mast cell-dependent granulocyte infiltration by the N-terminal peptide is enhanced by the activation of vascular endothelial cells by the C-terminal peptide. 137 Sep 26

To determine whether the N-terminal or C-terminal peptide of substance P (SP) induces granulocyte infiltration in mouse skin, we examined the potencies of SP, the N-terminal peptides SP1-4 and SP1-9, the C-terminal peptides SP4-11 and SP6-11, and a mast cell degranulating agent compound 48/80 in inducing granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice. The subcutaneous administration of SP (10(-7)-10(-5) M) caused granulocyte infiltration in mouse skin in a concentration-dependent fashion 6 h after the injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration in the skin which was associated with mast cell degranulation. However, SP1-4, SP4-11 and SP6-11 (up to 10(-4) M) induced neither granulocyte infiltration nor mast cell degranulation. In addition, compound 48/80 (0.5-50 micrograms/ml) also induced granulocyte infiltration of mouse skin with a concentration-dependent increase in mast cell degranulation. These results indicate that SP induces granulocyte infiltration of mouse skin through mast cell degranulation induced by the N-terminal peptide.
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PMID:[The potencies of substance P, substance P fragments, and compound 48/80 for granulocyte infiltration in mouse skin]. 137 99

It has recently been shown that substance P induces neutrophil infiltration in the skin, which is mediated through mast cell degranulation. Since substance P activates both skin mast cells and vascular endothelial cells, we compared the potencies of substance P and a mast cell-degranulating agent, compound 48/80, which is inactive for vascular endothelial cells, in inducing neutrophil infiltration in mouse skin. We also examined the effect of the C-terminal peptide of substance P, SP6-11, which is active for vascular endothelial cells, on compound 48/80-induced neutrophil infiltration in the skin. Subcutaneous administrations of substance P (10(-7) to 10(-5) M; 0.1 ml) and compound 48/80 (0.5-50 micrograms/ml) induced neutrophil infiltrations and mast cell degranulations in mouse skin in a concentration-dependent fashion. Moreover, substance P induced more neutrophil infiltrations than compound 48/80 in terms of the magnitude of mast cell degranulations. SP6-11 (10(-6) to 10(-4) M) induced no significant neutrophil infiltration or mast cell degranulation, but increased the vascular permeability of endothelial cells in the skin. Furthermore, SP6-11 enhanced compound 48/80-induced neutrophil infiltration without any increase in mast cell degranulation. Our results indicate that, in addition to mast cell degranulation, the activation of vascular endothelial cells is involved in substance P-induced neutrophil infiltration in the skin.
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PMID:Comparison of substance P-induced and compound 48/80-induced neutrophil infiltrations in mouse skin. 137 5

The sialogogic response of submandibular glands to analogs of the C-terminal hexapeptide of substance P with various amino acids at the N-terminus was investigated in urethane-anesthetized rats. The rank order of potencies was as follows: SP greater than (pGlu6)SP6-11 much greater than (Dab6)SP6-11 greater than (Orn6)SP6-11 greater than (Gln6)SP6-11 greater than (Lys6)SP6-11 much greater than (Ala6)SP6-11. These results suggest that the sialogogic activity of the analogs of the C-terminal hexapeptide is influenced by the steric effects of the N-terminal amino acid, and the nature of its side chain is of particular importance.
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PMID:Sialogogic effects on rat submandibular gland of analogs of the C-terminal hexapeptide of substance P. 138 Oct 1

To investigate the role of neuropeptides in allergic inflammation, we examined the effect of peptides on eosinophil chemotaxis. Eosinophils were purified from the blood of allergic and normal subjects using a discontinuous Percoll density gradients. Chemotaxis was induced by platelet-activating factor (PAF) and leukotriene B4, and was assayed by a modified Boyden's chamber technique. Four neuropeptides were examined in this study: substance P (SP), neurokinin A, calcitonin gene-related peptide (CGRP), and cholecystokinin octapeptide. Peptides alone (10 nM to 10 microM) were not chemotactic for eosinophils. However, when eosinophils were pre-treated with peptides (100 nM) at 37 degrees C for 30 min, chemotactic response to PAF (10 nM) was significantly enhanced (p < 0.01) in allergic subjects; % control by SP, neurokinin A, CGRP and cholecystokinin octapeptide was 269 +/- 42, 243 +/- 32, 227 +/- 21, and 251 +/- 42, respectively (n = 8). Similar results were obtained in leukotriene B4-induced eosinophil chemotaxis. In contrast, no enhancement was observed in normal subjects. Potentiating effect of SP and CGRP on PAF-induced eosinophil chemotaxis in allergic subjects was significantly attenuated by SP antagonist [D-Pro2,D-Trp7,9]-SP and human CGRP (8-37) receptor antagonist, respectively. Neutral endopeptidase inhibitors (phosphoramidon, leupeptin, and bestatin) failed to significantly augment the PAF-induced eosinophil chemotaxis when the cells were pretreated with various peptides and neutral endopeptidase inhibitors. The C-terminal fragment of SP (SP6-11) had an effect similar to that of the intact SP molecule, whereas no potentiating effect by the N-terminal of SP (SP1-9) was observed. These results suggest that neuropeptides may play a significant role in eosinophil infiltration by priming cells in allergic inflammation.
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PMID:Neuropeptides modulate human eosinophil chemotaxis. 138 21

A new glycopeptide analogue of substance P (6-11) (SP6-11), namely, N1,6 (beta-D-glucopyranosyl) [Glu6, Pro9]SP6-11, has been synthesized and found to be water soluble. The in vitro biological activity of this glycopeptide was determined for spasmogenic activity in the guinea pig ileum and for potentiation of electrically evoked contractions in the rat vas deferens. Thus, activities on NK-1, NK-2, and NK-3 receptor types have been differentiated by two assays and, in the case of NK-1 and NK-3, receptors in guinea pig ileum (GPI) were assayed using specific pharmacological procedures. The ED50 values for the analogue and reference peptides substance P (SP), neurokinin A(NKA), and neurokinin B (NKB) were determined and potencies relative to SP were calculated. The analogue is three times more potent than the potent NK-1 agonist SP on NK-1 receptors. Moreover, this glycopeptide proved to be as selective for the NK-1 receptor as the specific agonist SPOMe (the methyl ester of substance P).
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PMID:A synthetic glycopeptide of substance P analogue (SP6-11) with enhanced NK-1 receptor specificity. 169 Feb 89

Reinforcing effects of intraperitoneally (IP) administered substance P (SP1-11), its amino-terminal fragment SP1-7 (SPN) and an analog of the carboxy terminus (pGlu6-SP6-11: SPC) were studied in rats. Two conditioned place preference paradigms were used. After three pairings of the drug with a certain environment the effect of the treatment was evaluated in the drug-free state during a test trial. The reinforcing effects of SP (37 nmol) and the equimolar dose of SPC were expressed by a significant increase in the amount of time the animals spent in the treatment environment. Other doses of SP (3.7 and 185 nmol) and SPC (7.4 and 185 nmol) and none of the doses of SPN (37, 185, 370 nmol) influenced the place preference behavior of the rats. The reinforcing effects of SP parallel the known facilitating effects of peripherally administered SP on memory. The amino acids that encode the reinforcing effects of SP may lie within the C-terminal sequence of the SP molecule.
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PMID:Reinforcing effects of peripherally administered substance P and its C-terminal sequence pGlu6-SP6-11 in the rat. 169 Apr 33

Substance P (SP) is believed to be a major mediator of neurogenic inflammation. To determine whether the skin reactivity of SP is increased in asthmatics, we examined the reactivity to intradermal injections of SP, the C-terminal and N-terminal peptides SP6-11 and SP1-9, respectively, and neurokinin A (10(-7)-10(-5) M) in 12 asthmatics and 9 normal subjects. SP and the N-terminal peptide SP1-9 induced both erythemas and wheals in asthmatics and in normal subjects, whereas the C-terminal peptide SP6-11 and neurokinin A primarily induced only wheals in both groups. SP induced greater erythemas and wheals in asthmatics than in normal subjects. SP1-9 also induced greater erythemas and wheals in asthmatics than in normal subjects. However, the wheals induced by SP6-11 or neurokinin A were not significantly different in either group. Therefore, the increased skin reactivity to SP was the N-terminal peptide dependent, which has been shown to be able to activate skin mast cells. We conclude that the skin reactivity to SP is increased in asthmatics, possibly through the increased reactivity of skin mast cells.
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PMID:[Skin reactivity to substance P in asthmatics]. 169 94

The in vitro influence of substance P (SP) C- and N-terminal fragments on the Na+,K(+)-ATPase and Ca2+,Mg2(+)-ATPase and monoamine oxidase (MAO) from synaptosomal membrane and extra-synaptosomal mitochondria were studied. The obtained results indicate: 1. C-terminal fragment of SP (SP6-11) in 10 microM concentration stimulates the Ca2+,Mg2(+)-ATPase activities from cerebral cortex and hippocampus. Na+,K(+)-ATPase from cerebral cortex is hardly sensitive to the action of this fragment. 2. N-terminal fragment of SP (SP1-5) in 10 microM concentration increases Na+,K(+)-ATPase activity from cerebral cortex and hippocampus. 3. N-terminal tetrapeptide (SP1-4) exerts no influence on ATPases independently from their brain localization. 4. The activity of monoamine oxidase after use of C- and N-terminal fragments is unchanged.
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PMID:Effects of N- and C-terminal fragments of substance P on ATPase and monoamine oxidase activities in rat brain. 169 30

1. Whole-cell patch-clamp recordings were made from pairs of neurones in cell cultures of rat myenteric neurones. In some pairs, action potentials evoked in the first neurone evoked a slow excitatory postsynaptic potential (EPSP) in the second neurone. 2. Action potentials at a frequency of at least 5 Hz were required to evoked slow EPSPs. In one group of cells, the slow EPSP followed a series of nicotinic fast EPSPs; in another group, fast EPSPs did not precede the slow EPSP. 3. The slow EPSPs were 2-16 mV in amplitude and were accompanied by decreased resting potassium conductance. 4. Most (17/28) neurones in which action potentials evoked only slow EPSPs in a follower cell contained substance P (SP)-like immunoreactivity; they were not immunoreactive for 5-hydroxytryptamine (0/15) or vasoactive intestinal peptide (0/22). 5. Postsynaptic responses to SP, neurokinin A and a synthetic tachykinin [( pGlu6, Pro9]SP6-11) mimicked the slow EPSPs. The non-tachykinin peptide vasoactive intestinal polypeptide (VIP), which was not found in neurones that evoked only slow EPSPs, also mimicked the slow EPSPs. Responsiveness to SP decreased significantly during slow EPSPs. 6. Desensitization to either SP or VIP reduced or prevented the slow EPSPs and also responses to each other. Two proposed antagonists of SP receptors, [D-Arg1, D-Pro2,D-Trp7,9,Leu11]substance P and [D-Arg1,D-Trp7,9,Leu11]substance P, did not affect the slow EPSPs significantly. 7. Antisera against SP reversibly blocked or reduced slow EPSPs evoked by eight of thirteen presynaptic neurones that evoked slow EPSPs without evoking fast EPSPs. All eight of the presynaptic neurones that evoked anti-SP-sensitive slow EPSPs contained SP-like immunoreactivity. None of the presynaptic neurones that evoked anti-SP-insensitive slow EPSPs contained detectable SP-like immunoreactivity. Normal sera and anti-VIP antisera did not alter the slow EPSPs detectably. 8. It is concluded that subsets of myenteric neurones release an SP-like transmitter to evoke slow EPSPs. These neurones appear to lack a 'classical' neurotransmitter that evokes fast EPSPs.
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PMID:Substance P mediates synaptic transmission between rat myenteric neurones in cell culture. 170 Jan 7


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