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)

Neuropeptides can influence immune effector cell function at both systemic and mucosal immune sites. We examined the ability of substance P (SP) to modulate the natural killer (NK) activity of intestinal intraepithelial leucocytes (IEL). Yac-1 killing by IEL but not splenic cells was increased after either 18 hr preincubation or 6 hr of co-incubation with SP. We also examined the NK activity of IEL and spleen isolated from mice treated with SP in vivo. The selective increase in NK activity of IEL occurred without any demonstrable change in the number or phenotype of the IEL. The IEL responsive to SP in vivo and induced in vivo by SP were both Thy-1- and did not kill the NK insensitive mastocytoma cell line P815. Lastly, we examined the ability of SP to induce the release of interleukin-2 (IL-2) and IL-4 from IEL after 6 and 18 hr of in vitro culture. No increase in the release of these cytokines was observed, suggesting that IL-2 and IL4 are not involved in the local augmentation of IEL NK activity by SP. These observations suggest that SP has a selective stimulatory effect on intestinal activity and may play a role in the regulation of intestinal cell-mediated immunity.
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PMID:Selective modulation of the natural killer activity of murine intestinal intraepithelial leucocytes by the neuropeptide substance P. 169 80

Sodium-butyrate-pretreated and Con A-stimulated P815 mast cell line generated 3T3 fibroblast proliferating activity. This fibroblast stimulatory activity was partially abrogated by three different substance P antagonists such as spantide (NK1 antagonist), FK224 (NK1 and NK2 antagonist) or FK888 (NK1 antagonist) or anti-substance P antibody. In addition to P815 mastocytoma cell, IL3-dependent, bone marrow-derived mast cells also generated fibroblast proliferating activity which was also partially abrogated by substance P antagonists. Anti-fibrogenic cytokine antibodies also inhibited mast cell-derived fibroblast proliferating activity. Substance P or histamine augmented fibrogenic cytokine-induced fibroblast proliferation which indicates that mast cell-derived histamine or substance P play an important role in induction of tissue fibrosis in fibrosing diseases.
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PMID:Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis. 930 48

We investigated the effect of aqueous extract of Soloanum lyratum THUNB. (Solanaceae) (SLAE) on anaphylactic reaction. The mast cell is widely thought to contribute to the acute changes associated with anaphylaxis. SLAE inhibited skin mast cells-mediated anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. SLAE dose-dependently inhibited histamine release in mouse peritoneal mast cells activated by anti-DNP IgE or substance P. Substance P increased steady state levels of L-histidine decarboxylase (HDC) mRNA in mouse mastocytoma P-815 cells. Northern-blot analysis demonstrated that significantly reduced level of the mRNA of HDC was expressed in mast cells treated with SLAE, compared to that without SLAE. We conclude that SLAE directly affect IgE-mediated anaphylactic reaction and substance P-induced HDC mRNA over-expression.
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PMID:Solanum lyratum inhibits anaphylactic reaction and suppresses the expression of L-histidine decarboxylase mRNA. 954 4

Dipeptidyl peptidase I (DPPI) is a cysteine protease found predominantly in myelomonocytic cells, cytotoxic T-cells, and mast cells. Recent studies identify an intracellular role for mast cell-DPPI (MC-DPPI) by activating prochymase and protryptase to their mature forms. To better define MC-DPPI and to explore the possibility of extracellular roles, we purified MC-DPPI from mastocytoma cells. We found the dog C2 mastocytoma cell line to be the richest source yet described for DPPI, purifying up to 200 microg of enzyme per g of cells. Dog MC-DPPI has an Mr of approximately 175,000 and consists of four subunits, each composed of a propeptide, light chain, and heavy chain. The heavy chain is N-glycosylated and is heterogeneously processed to three different forms. NH2-terminal sequences of the heavy chain and propeptide are identical to those predicted from a cDNA clone we sequenced from a mastocytoma cDNA library. The dog cDNA-derived sequence is 86% identical to that of human DPPI. Dog mastocytoma cells incubated with 12-O-tetradecanoylphorbol-13-acetate increase expression of MC-DPPI mRNA. MC-DPPI maintains its activity for dipeptide substrates at a neutral to alkaline pH. Cells stimulated with ionophore or substance P secrete MC-DPPI in parallel with the granule-associated mediators tryptase and histamine. Thus, dog mastocytoma cells secrete DPPI that is active at the pH of extracellular fluids, suggesting that MC-DPPI may act outside the cell.
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PMID:Regulated expression, processing, and secretion of dog mast cell dipeptidyl peptidase I. 962 39

The dog mastocytoma BR cell line provides us with a permanent source of canine mast cells, allowing a characterization of secretory mediators that exert important effects in canine allergic and nonallergic diseases and in physiological processes. We studied the ultrastructural characteristics and histamine releasing activity after immunological and non-immunological stimuli of the dog mastocytoma BR cell line, and compared the cell line to normal skin mast cells enzymatically isolated from healthy dogs. The histamine content of BR cells was 0.04 +/- 0.002 pg/cell, approximately 100-fold less than that found in canine skin mast cells. Non-immunologic stimuli induced similar concentration-dependent histamine release from skin mast cells and BR cells: 29.3 +/- 0.9% vs. 12.7 +/- 0.7% (calcium ionophore A23187), 23.3 +/- 0.7% vs. 18.8 +/- 0.7% (substance P) and 12.5 +/- 0.3% vs. 12.1 +/- 0.9% (compound 48/80), respectively. Immunologic stimulation, however, was only effective on canine skin mast cells, causing 30.9 +/- 1.7%, 27.7 +/- 0.6% and 12.2 +/- 0.9% histamine release in response to anti-canine IgE, concanavalin A, and antigen Asc S 1, respectively. The absence of functional IgE receptors in BR cells was confirmed by the lack of response to anti-IgE and antigen Asc S 1 following passive sensitization with dog atopic serum and dog antigen sensitized serum. We conclude that BR cells are able to release histamine after non-immunologic stimulation in a similar manner to canine skin mast cells, but that there are morphological and functional differences possibly due to different states of maturity or differentiation. For this reason the study of the highly homogeneous BR cells could offer insights into dog mast cell biology in contexts where freshly isolated cells cannot be used because of low purity and recovery.
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PMID:Comparative morphofunctional study of dispersed mature canine cutaneous mast cells and BR cells, a poorly differentiated mast cell line from a dog subcutaneous mastocytoma. 964 37

1 Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. 2 The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. 3 The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. 4 Tachykinin NK(1) receptor antagonists, [D-Pro(2), D-Trp(7,9)]-SP, [D-Pro(4), D-Trp(7,9)]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK(1) receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. 5 The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP(8-37)). 6 The toxin-induced leakage was significantly inhibited by the N-type Ca(2+) channel blocker, omega-conotoxin MVIIA, and the bradykinin B(2) receptor antagonist, HOE140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin), but was not affected by the selective L-type Ca(2+) channel blocker, verapamil, the P-type Ca(2+) channel blocker, omega-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na(+) channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. 7 These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK(1) receptors.
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PMID:Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation. 1252 69