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)

Pancreozymin in man as in animals appears to act as a specific enzyme stimulant. The preparations of pancreozymin used in these experiments also contain cholecystokinin, which causes the gall bladder to contract, and a smooth muscle stimulant, possibly substance P. The duodenal contents obtained in response to a standard dose of secretin and pancreozymin have been collected quantitatively in man and the volume and amount of bicarbonate, amylase, trypsin, and lipase measured in order to study pancreatic function. The results of 105 tests undertaken on a normal group, in pancreatic and biliary disease, and in non-pancreatic steatorrhoea have been analysed. In localized pancreatic lesions and after recovery from acute pancreatitis, normal function is often retained. Mild functional impairment may be demonstrated only by a poor enzyme output in the post-pancreozymin fractions, while at a later stage bicarbonate output is affected and finally the volume of the duodenal contents is reduced. The secretin-pancreozymin test is most valuable, therefore, in the more chronic and advanced forms of pancreatic disease in which it gives a good assessment of residual pancreatic function. In diagnosis care must be taken in interpreting a functional test in terms of anatomical pathology. The test has proved useful not only in diagnosis but also as a guide to treatment and an index of prognosis.
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PMID:A test of pancreatic function in man based on the analysis of duodenal contents after administration of secretin and pancreozymin. 1380 39

Human mast cells are categorized into mast cells positive only for tryptase (MC(T)) and mast cells positive for both tryptase and chymase (MC(TC)). The structural appearance of tryptase-, and chymase-positive mast cells in metastatic liver disease and the variations in MC(T) and MC(TC) numbers in accordance with the origin of the primary tumors have been described in the present study. Liver mast cells are analyzed immunocytochemically using tryptase and chymase and by quantitative morphometry in 30 patients with colorectal (n = 15), gastric (n = 8), and pancreatic (n = 7) cancers and in 5 control livers. The numbers of MC(T) and MC(TC) are increased in the extratumoral liver tissue (mainly portal tracts) as compared to controls. The numbers of MC(T) and MC(TC) in and around metastases with moderate or high grade of differentiation are statistically significantly higher, as compared to those with low grades of differentiation. The numbers of MC(TC) are greater than that of MC(T) in the extratumoral liver tissue and in metastases themselves. Ultrastructurally, mast cells immunostained with tryptase and chymase have three types of granules: electron dense granules with darkly precipitated reaction product, electron lucent granules without reaction product and electron lucent granules with sparse reaction product (altered granules). Both types of mast cells have small and large in size granules, resembling the MC(TC) phenotype described earlier. Tryptase-positive mast cells have granules with discrete scrolls and particulate and beaded pattern. Chymase-positive mast cells have granules with finely granular or particulate material. Substance P (SP)- and vasointestinal polypeptide (VIP)-positive mast cells are not observed in livers with metastases. The present study suggests that liver mast cells are mainly from the MC(TC) type, and are accumulated in peritumoral and metastatic areas. They may play a role in the formation of tumor stroma, or in tumor immunology in liver metastases from various primary gastrointestinal cancers.
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PMID:Structural examination of tryptase- and chymase-positive mast cells in livers, containing metastases from gastrointestinal cancers. 1466 92

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.
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PMID:Key role of mast cells and their major secretory products in inflammatory bowel disease. 1476 Jul 48

Protease-activated receptors are G protein-coupled receptors activated by serine-proteases. Protease-activated receptor 2 is involved in the regulation of airway smooth muscle tone but its effects vary according to species and experimental conditions. We determined the effects of protease-activated receptor 2 activation on smooth muscle tone and airway reactivity to histamine in guinea pigs and smoking or non-smoking humans. The effects of trypsin and protease-activated receptor activating peptide on the isometric tension and response to histamine of guinea pig tracheal and human bronchial rings were studied. Human tissues were obtained from 6 smokers and 4 non-smokers. We assessed the effects of epithelial removal, inhibitors of cyclooxygenases, nitric oxide synthases, neutral endopeptidase and antagonists of acetylcholine, histamine, bradykinin and tachykinin receptors. Bronchomotor responses to protease-activated receptor 2 activation were variable in guinea pig, in half of animals PAR2 activation induced smooth muscle relaxation through the epithelial release of prostanoids but not of nitric oxide. In human airways, protease-activated receptor 2 activation reduced responsiveness to histamine in bronchial rings from smokers but increased responsiveness in bronchi from non-smokers. This study demonstrates an influence of tobacco smoking on the effect of protease-activated receptor 2 activation on airway responsiveness in humans, with an increased protection against histamine-induced contractions, probably through an increased epithelial release of prostanoids. The role of airway protease-activated receptor 2 may be to maintain smooth muscle tone homeostasis.
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PMID:Protease-activated receptor 2 in regulation of bronchomotor tone: effect of tobacco smoking. 1519 59

Chronic liver diseases commonly result in liver fibrosis, and eventually liver cirrhosis. In the last decade, a new theory explaining liver fibrosis has been established. Accordingly, the development of liver fibrosis due to chronic liver diseases is thought to be mediated by inflammatory cells. They release fibrogenic mediators such as transforming growth factors (TGF)-beta, which are considered to be responsible for the activation and transformation of fat-storing cells. Recently, the involvement of mast cells and peripheral and autonomic nervous system in the fibrogenesis has been suggested. This study was aimed to establish the presence and distribution of mast cells and nerve fibers in the rat liver in the light of their implication in liver inflammatory and fibrotic disorders. Mast cells and afferent (sensory) fibers were detected immunohistochemically. An immunofluorescent method was applied to demonstrate tryptase and serotonin (SER) in the mast cells, while the primary sensory neuronal processes were identified by using antibodies against their marker calcitonin gene-related peptide (CGRP) and the proinflammatory mediator substance P (SP). The portal tracts and fibrous septa contained numerous mast cells, which exhibited strong immuno-reactivity to tryptase and SER. SER-positive nerve fibers were also found. It is generally accepted that no nerve fibers are present in the hepatic lobules, but the current investigation clearly demonstrates availability of CGRP-, SP, and SER-immunoreactive nerve fibers there. Our results indicate that in the rat liver portal tracts and hepatic lobules there are numerous mast cells, sensory and autonomic nerve fibers, which may be involved in liver injury by the inflammatory mediators they release.
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PMID:Relevance of mast cells and hepatic lobule innervation to liver injury. 1547 May 32

Stimulation of primary sensory neurons produces local vasodilation, plasma extravasation, and pain and is due largely to the release of the tachykinins substance P and calcitonin-gene-related peptide. Pathological activation of sensory neurons and the inflammatory sequelae are known as neurogenic inflammation and appear to be important in many organ systems, including the pancreas. Factors that stimulate primary sensory neurons include hydrogen ions, heat, leukotrienes, arachidonic acid metabolites, bradykinin, and proteases such as trypsin, all of which may participate in the generation of acute pancreatitis. The current review examines the cellular and molecular mechanisms involved in sensory nerve activation within the pancreas and the potential contribution of neurogenic inflammation to the pathogenesis of pancreatitis.
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PMID:Neurogenic inflammation and pancreatitis. 1555 Jul 64

Surgical biopsy specimens obtained from 50 patients with secondary cholangitis caused by obstruction of the common bile duct were studied immunohistochemically. Data on the number and ultrastructural appearances of mast cells positive for tryptase, chymase, vasointestinal polypeptide (VIP), and substance P (SP) were obtained. The bile ducts from patients presenting combined chronic exacerbated cholangitis and chronic sclerotic cholangitis showed significantly higher numbers of mast cell types compared to the controls (P < 0.0001). Cases with sclerotic cholangitis alone had significantly lower number of cells than patients with chronic exacerbated cholangitis alone (P < or = 0.0001). Morphometric measurements of electron micrographs showed that mast cell granules containing VIP, SP and chymase were commensurable in size. Electron-lucent granules without reaction product (altered granules) and granules with focal distribution of the reaction product were observed in all types of mast cells. Furthermore, some nerve fibers positive for SP and VIP and serotonin-positive endocrine cells were observed in close proximity to the mast cells. In conclusion, the results of our study demonstrate the existence of different populations of mast cells, nerve structures and endocrine cells in the lower part of the human large bile duct, and suggest their participation in the development of pathological processes.
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PMID:Mast cells in human bile duct obstruction. 1560 92

Dental pulp inflammation often results from dissemination of periodontitis caused mostly by Porphyromonas gingivalis infection. Calcitonin gene-related peptide and substance P are proinflammatory neuropeptides that increase in inflamed pulp tissue. To study an involvement of the periodontitis pathogen and neuropeptides in pulp inflammation, we investigated human dental pulp cell neuropeptide release by arginine-specific cysteine protease (RgpB), a cysteine proteinase of P. gingivalis, and participating signaling pathways. RgpB induced neuropeptide release from cultured human pulp cells (HPCs) in a proteolytic activity-dependent manner at a range of 12.5-200 nM. HPCs expressed both mRNA and the products of calcitonin gene-related peptide, substance P, and proteinase-activated receptor-2 (PAR-2) that were also found in dental pulp fibroblast-like cells. The PAR-2 agonists, SLIGKV and trypsin, also induced neuropeptide release from HPCs, and HPC PAR-2 gene knockout by transfection of PAR-2 antisense oligonucleotides inhibited significantly the RgpB-elicited neuropeptide release. These results indicated that RgpB-induced neuropeptide release was dependent on PAR-2 activation. The kinase inhibitor profile on the RgpB-neuropeptide release from HPC revealed a new PAR-2 signaling pathway that was mediated by p38 MAPK and activated transcription factor-2 activation, in addition to the PAR-2-p44/42 p38MAPK and -AP-1 pathway. This new RgpB activity suggests a possible link between periodontitis and pulp inflammation, which may be modulated by neuropeptides released in the lesion.
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PMID:Neuropeptide release from dental pulp cells by RgpB via proteinase-activated receptor-2 signaling. 1584 83

Protease-activated receptor 2 (PAR2) is activated by trypsin and mast cell tryptase to induce widespread inflammation by unknown mechanisms. Trypsin and tryptase were shown to activate sensory neurons to release substance-P and related peptides to mediate neurogenic inflammation. In the present study, the expression of PAR2 and tachykinins were investigated in rat trigeminal neurons that were identified by retrograde labeling with rhodamine dye from the nasal mucosa by using neuronal tracing in combination with immunohistochemistry. We found that large subpopulation of all trigeminal neurons (43.5+/-2.6%) identified by the pan-neuronal marker PGP 9.5 were stained with PAR2-immunoreactivity. Of all trigeminal neurons, 7.5+/-2.1% were immunoreactive for tachykinins and PAR2, and only 3.9+/-1.7% of all trigeminal neurons expressed tachykinins, but not PAR2-immunoreactivity. The present study also found that a large number trigeminal neurons innervating the nasal mucosa expressed PAR2-immunoreactivity. Of the rhodamine-labeled trigeminal neurons, 52.5+/-1.8% were immunoreactive for only PAR2 expression, 7.3+/-1.9% contained tachykinins and PAR2, and 3.1+/-0.4 of the rhodamine-labeled trigeminal neurons were non-immunoreactive PAR2, but were positive for tachykinins-immunoreactivity. In conclusion, based on the co-localization of PAR2 and tachykinins in trigeminal sensory neurons innervating the nasal mucosa, the present study suggests that, following an activation of PAR2 receptor in tachykinergic neurons by trypsin and mast cell tryptase, there may be a triggering of tachykinin-mediated phenomena such as neurogenic inflammation in allergic or non-allergic rhinitis.
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PMID:Protease-activated receptor 2 expression in trigeminal neurons innervating the rat nasal mucosa. 1615 Apr 84

Activation of protease-activated receptors (PAR) can induce vasodilation (VD) and increase of vascular permeability either directly by stimulating endothelial cells or indirectly via activation of nociceptors and subsequent release of neuropeptides (neurogenic inflammation). We aimed to estimate the relative contribution of the two pathways for stimulation with endogenous activators of PAR-2 (trypsin) and of PAR-1, 3 and 4 (thrombin) using in vivo dermal microdialysis in rats. Protein extravasation (PE) was assessed by increase of protein concentration in the dialysate, and VD was quantified by laser Doppler scanning. Both trypsin (10(-8)-10(-4) M) and thrombin (10(-6), 10(-5.5) and 10(-5) M) provoked PE and local VD in a dose-dependent manner. Trypsin (10(-4) M)-induced PE was inhibited by 87.2 +/- 21% due to the substance P (SP) NK1 receptor antagonist SR140333. VD was blocked by 58.15 +/- 10.1% in response to the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37). By contrast, CGRP(8-37) did not affect thrombin-induced VD, while blockade of SP receptors prevented the PE elicited only by low doses of thrombin (10(-6) M), being ineffective at higher thrombin concentrations. In conclusion, intradermal trypsin elicits a neurogenic inflammation in rat, probably mediated via PAR-2 activation on nociceptors and subsequent SP and CGRP release. Thrombin-induced PE and VD are mediated mainly by a non-neurogenic mechanism.
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PMID:Neurogenic components of trypsin- and thrombin-induced inflammation in rat skin, in vivo. 1636 32


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