Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of endothelin (ET)-containing mast cells was immunohistochemically investigated in the rat lung and gastrointestinal tract using antibodies against Big ET-1, Big ET-2, Big ET-3, mature ETs and their receptors of ET-A, and ET-B. In the lung, numerous mature ETs-containing mast cells were present in connective tissue around the bronchus, bronchioles and in the interalveolar septa. The number of Big ET-2-containing mast cells was almost the same as that of Big ET-3-containing mast cells, while Big ET-1-positive mast cells were fewer than that of the other isopeptides. In all the regions of the gastrointestinal tract, immunoreactivity for mature ETs was found mainly in mast cells of the lamina propria, the number of Big ET-2 and Big ET-3-containing cells was almost the same similar to that found in the lung, while Big ET-1-containing cells were very few. Moreover, mast cells in not only lung but also gastrointestinal tract contain both of ET-A and ET-B receptors. Electron-microscopically, ET-immunoreaction products were mainly precipitated in the mast cell granules. Hence, we presume that ETs are synthesized in and secreted from mast cells in the rat lung and gastrointestinal tract; they act in an autocrine/paracrine fashion; and their main isopeptides are ET-2 and ET-3.
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PMID:[Immunocytochemical studies on the endothelin peptides and their receptors in mast cells of the rat lung and gastrointestinal tract]. 977 20

Mast cells have been shown to produce endothelin-1 (ET-1) and to express ET receptors. Thus, we postulated that ETs modulate mast cell mediator production in an autocrine manner. Rat tissue-cultured mast cells (RCMC-1) were incubated with exogenous ET-1 or ET-3, and beta-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1alpha (MIP-1alpha), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of beta-hexosaminidase and TNF and of mRNA expression. An antagonist of the ET(B) receptor subtype abrogated ET-stimulated TNF release, although ET(A) and ET(B) receptors have been identified by immunocytochemistry. It is interesting that ET-1 and ET-3 inhibited (25-30%) mRNA expression of Th2-type cytokines (IL-4, IL-10, and IL-13) and increased IL-12 release (39% and 41%, respectively) without affecting MIP-1alpha and NO production. Thus, our data suggest that ETs may play an important role in modulating the cytokine network by regulating Th1/Th2 cytokine production by mast cells.
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PMID:Endothelins regulate mediator production of rat tissue-cultured mucosal mast cells. Up-regulation of Th1 and inhibition of Th2 cytokines. 1199 8

The effects of endothelin-1 (ET-1) on mucosal mast cells are of special interest, since they may be an important component of the tissue response that occurs during ischaemic preconditioning or ischaemia/re-oxygenation injuries. Increasing doses of ET-1 were administered intravenously to anaesthetized rats. In a second series of experiments, animals were pretreated with the ET(A) receptor antagonists BQ-610 or ETR-P1/fl peptide, or with the ET(B) receptor antagonist IRL-1038. Intestinal perfusion changes were recorded, and the proportion of degranulated mast cells and the degree of mucosal damage were determined in ileal biopsies. ET-1 induced dose-dependent alterations in the haemodynamic and morphological parameters, and caused significant mast cell degranulation. These changes were inhibited significantly by pretreatment with the ET(A) receptor antagonists, but not with the ET(B) receptor antagonist. We conclude that a cross-talk exists between endothelial cell-derived humoral mediators and the intestinal mast cell system.
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PMID:Endothelin-1 induces mucosal mast cell degranulation and tissue injury via ETA receptors. 1219 49

The objective of this study was to investigate the effect a nonselective endothelin-1 (ET-1) receptor antagonist (bosentan) had on the acute myocardial remodeling process including left ventricular (LV) mast cells and matrix metalloproteinase (MMP) activity secondary to volume overload. Additionally, we investigated the overall functional outcome of preventative endothelin receptor antagonism during 14 days of chronic volume overload. LV tissue from sham-operated (Sham), untreated-fistula (Fist), and bosentan (100 mg.kg(-1).day(-1))-treated animals (Fist + Bos) was analyzed for mast cell density, MMP activity, and myocardial collagen volume fraction at 1 and 5 days after the creation of an aortocaval fistula. When compared with untreated fistulas, bosentan treatment prevented the marked increase in LV mast cell density at 1 day postfistula (3.1 +/- 0.3 vs. 1.3 +/- 0.3 LV mast cells/mm2, Fist vs. Fist + Bos, P <or= 0.01). Additionally, the substantial increase in MMP-2 activation in the untreated fistula at 1 day was prevented following bosentan treatment (1.6 +/- 0.3 vs. 0.9 +/- 0.1 arbitrary activity units, Fist vs. Fist + Bos, P <or= 0.01). The marked decrease in collagen volume fraction seen in the Fist group (1.4 +/- 0.1 vs. 0.8 +/- 0.1% myocardial tissue, Sham vs. Fist, P <or= 0.01) was significantly attenuated following bosentan treatment at both the 1- and 5-day time points. Lastly, a 2-wk preventative treatment with bosentan resulted in significant attenuation of the increase in LV end-systolic and -diastolic volumes compared with those in untreated fistula hearts. In summary, nonselective ET-1 antagonism prevents the acute increases in cardiac mast cell density and MMP activation induced secondary to chronic volume overload. By preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits in the first 2 wk of chronic volume overload. Accordingly, these results are the first to demonstrate that cardiac mast cells are responsive to the endogenous endothelin system in vivo. Another novel finding from this study is that chronic nonspecific endothelin antagonism may inadvertently potentiate ET-1-mediated signaling.
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PMID:Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats. 1817 27

The objective of this study was to investigate the ability of selective endothelin receptor subtype A (ET(A)) endothelin receptor antagonism (ETA) to prevent the acute myocardial remodeling process secondary to volume overload. Left ventricular tissue from sham-operated (Sham) and untreated (Fist), and TBC-3214 (Fist + ETA, 25 mg.kg(-1).day(-1))-treated fistula animals was analyzed for mast cell density, matrix metalloproteinase (MMP) activity, and extracellular collagen volume fraction (CVF) 1 and 5 days following the initiation of volume overload. Compared with Fist, ETA treatment prevented the increase in left ventricular mast cell density at 1 day and 5 days. Additionally, at 1 day postfistula, a substantial decrease in MMP-2 activity below Sham levels was observed following endothelin receptor antagonism (1.7 +/- 0.7 vs. 0.3 +/- 0.3 vs. 0.9 +/- 0.2 arbitrary activity units, Fist vs. Fist + ETA vs. Sham, P < or = 0.05). This same effect was also seen at 5 days postfistula (1.9 +/- 0.3 vs. 0.5 +/- 0.1 arbitrary activity units, Fist vs. Fist + ETA, P < or = 0.05). The marked decrease in myocardial CVF seen in Fist hearts (0.7 +/- 0.1 vs. 1.6 +/- 0.1% myocardial area, Fist vs. Sham, P < or = 0.05) was prevented by ETA (1.7 +/- 0.1% Fist + ETA, P < 0.05 vs. Fist). This preservation of the collagen matrix was also present on day 5 in the TBC-treated group vs. the Fist group (1.0 +/- 0.1 vs. 1.4 +/- 0.1%, Fist vs. Fist + ETA, P < or = 0.01). Furthermore, an 8-wk preventative treatment with ETA significantly attenuated the increase in left ventricular end systolic and diastolic volumes compared with untreated fistula hearts. In conclusion, the novel findings of this study indicate that the activation of cardiac mast cells and subsequent MMP activation/collagen degradation during the acute stages of volume overload are prevented by blockade of the ET(A) receptor subtype. Furthermore, by preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits.
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PMID:ETA selective receptor antagonism prevents ventricular remodeling in volume-overloaded rats. 1942 17