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)

Substance P (SP) induces increased vascular permeability, vasodilatation and granulocyte infiltration upon intradermal injection. Studies with antagonists and mast cell-deficient mice have suggested that granulocyte infiltration in response SP is mediated by leukotriene (LT) B4 derived from mast cells. However, the release of LTB4 has not been detected using mast cells isolated from human skin. Here we report the release of LTB4, prostaglandin (PG) D2 and histamine from guinea pig skin tissue in response to SP. The release of these agents occurred in a dose-dependent manner over a concentration range of SP from 1 x 10(-6) to 3 x 10(-4) M. No detectable PGE2 was released at any concentration up to 3 x 10(-4) M SP. The kinetics of histamine release induced in response to SP was more rapid than that induced by antigen. By comparison, SP-induced and antigen-induced release of LTB4 and PGD2 were similar, but slower than the histamine release. In the absence of extracellular Ca2+, release of histamine and PGD2 in response to SP was partially impaired, but to a lesser extent than that induced by antigen. On the other hand, LTB4 release in response to both SP and antigen was abolished under the same conditions. These results indicate that SP induces the release of LTB4, as well as histamine and PGD2, in the skin most likely from mast cells by a mechanism which may be different from that of mediator release in response to antigen.
 ...
PMID:Substance P- and antigen-induced release of leukotriene B4, prostaglandin D2 and histamine from guinea pig skin by different mechanisms in vitro. 1048 19

Historically, mast cells were known as a key cell type involved in type I hypersensitivity. Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the ileum and colon of patients with IBD, which was accompanied by great changes of the content in mast cells such as dramatically increased expression of TNFalpha, IL-16 and substance P. The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of patients with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD. However, little is known of the actions of histamine, tryptase, chymase and carboxypeptidase in IBD. Over the last decade, heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the patients showed good clinical and laboratory response with no serious adverse effects. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. The hypothesis is that mast cell secretogogues induce mast cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H1 receptor. Whereas released tryptase acts similarly to histamine, but activates mast cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the pathogenesis of IBD. In conclusion, while pathogenesis of IBD remains unclear, the key role of mast cells in this group of diseases demonstrated in the current review implicates strongly that IBD is a mast cell associated disease. Therefore, close attentions should be paid to the role of mast cells in IBD.
 ...
PMID:Key role of mast cells and their major secretory products in inflammatory bowel disease. 1476 Jul 48

Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl) and deracoxib (Deramaxx) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs.
 ...
PMID:Characterization and modulation of canine mast cell derived eicosanoids. 2003 14

The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU. Off-licence uses of currently available drugs include rituximab and tumour necrosis factor inhibitors. Ligelizumab (anti-IgE), canakinumab (anti-IL-1), AZD1981 (a PGD2 receptor antagonist) and GSK 2646264 (a selective Syk inhibitor) are currently in clinical trials for CSU. Examples of drugs that could target potential pathophysiological targets in CSU include substance P antagonists, designed ankyrin repeat proteins, C5a/C5a receptor inhibitors, anti-IL-4, anti-IL-5 and anti-IL-13 and drugs that target inhibitory mast cell receptors. Other mediators and receptors of likely pathogenic relevance should be explored in skin profiling and functional proof of concept studies. The exploration of novel therapeutic targets for their role and relevance in CSU should help to achieve a better understanding of its etiopathogenesis.
 ...
PMID:Looking forward to new targeted treatments for chronic spontaneous urticaria. 2839 12

Basophils are blood granulocytes and normally constitute <1% of blood peripheral leucocytes. Basophils share some morphological and functional similarities with mast cells, and basophils were once regarded as redundant and negligible circulating mast cells. However, recent studies reveal the indispensable roles of basophils in various diseases, including allergic and pruritic diseases. Basophils may be involved in itch through the mediation of a Th2 immune response, interaction with other cells in the skin and secretion of a wide variety of itch-related mediators, for example histamine, cytokines and chemokines (IL-4, IL-13, IL-31 and TSLP), proteases (cathepsin S), prostaglandins (PGE2 and PGD2), substance P and platelet-activating factor. Not only pruritic skin diseases (eg, atopic dermatitis, irritant contact dermatitis, chronic urticaria, prurigo, papulo-erythroderma of Ofuji, eosinophilic pustular folliculitis, scabies, tick bites and bullous pemphigoid) but also pruritic systemic diseases (eg, primary sclerosing cholangitis and polycythemia vera) may be affected by basophils.
 ...
PMID:Possible roles of basophils in chronic itch. 2989 5


<< Previous 1 2 3