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

The IgE-mediated, antigen-induced release of histamine from human lung tissue causes profound changes in lung cyclic adenosine monophosphate and cyclic guanosine monophosphate. Exogenous histamine similarly induces increases in both cyclic nucleotides; pretreatment with H-1 antihistamines prevents the increase in cyclic guanosine monophosphate, whereas H-2 antihistamines prevent the increase in cyclic adenosine monophosphate. Anaphylaxis of human lung in vitro is unaffected by the presence of 1-100 micron histamine, H-1 antihistamines, H-2 antihistamines, or combinations of these agents despite the production of selective increases in total lung cyclic nucleotides. Futhermore, selective histamine agonists (2-methylhistamine [H-1 agonist] or dimaprit [H-2 agonist]) also fail to significantly influence the immunologic release of mediators. Histamine examined in the presence of ethylenediaminetetra-acetate was no more capable of modulating mediator release than when in the presence of calcium, in contrast to previous studies involving the human basophilic leukocyte. Therefore, the human lung mast cell is unresponsive to histamine with regard to modulating the antigen-induced, IgE-dependent, generation of mediators.
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PMID:Human lung tissue and anaphylaxis: the effects of histamine on the immunologic release of mediators. 8 41

Histamine is known to exert profound effects on the cardiovascular system in many mammals. Carnosine (beta-alanyl-L-histidine) is a dipeptide previously known to be present only in a few tissues. It is our hypothesis that carnosine serves as a non-mast cell reservoir for histidine, available for histamine synthesis during periods of physiologic stress. To validate this hypothesis, we demonstrated the existence of carnosine in multiple histamine-rich tissues in several mammalian species; documented a metabolic link between carnosine and histidine, histamine and 3-methylhistamine (a degradation product of histamine) in unstressed animals, and showed that tissue carnosine is decreased simultaneously with an increase in tissue histamine during stress.
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PMID:The presence and significance of carnosine in histamine-containing tissues of several mammalian species. 208 37

Carcinine (beta-alanylhistamine) is an imidazole dipeptide that exists in mammalian hearts, increases cardiac contractility, and is metabolically linked to carnosine (beta-alanylhistidine), a non-mast cell histidine and histamine precursor during stress. We have previously shown that tissue carnosine levels are regulated by H1 and H2 receptors. This study evaluated the effects of H1, H2, and mast cell degranulation blockers on metabolism of carcinine and related imidazoles during shock induced by compound 48/80, a mast cell degranulator. Fifty 125-g male Sprague-Dawley rats were divided into nine ip treatment groups: saline, 48/80, lodoxamide (LOD, mast cell degranulation inhibitor), diphenhydramine (DPH, H1 antagonist), cimetidine (CIM, H2 antagonist), LOD + 48/80, CIM + 48/80, DPH + 48/80, or DPH + CIM + 48/80. Heart tissue was analyzed at 30 min by HPLC. 48/80 caused decreases in myocardial carnosine (P less than 0.01) and histidine (P less than 0.0001) levels and concomitant increases in carcinine (P less than 0.01), histamine (P less than 0.01), and 3-methylhistamine (P less than 0.05) compared to those of controls. These changes were inhibited by LOD or DPH. Treatment with CIM significantly increased myocardial carcinine levels compared to 48/80 alone (P less than 0.001) without an additional effect on the other compounds. These data indicate that carcinine is involved in the cardiac response to stress via the carnosine-histidine-histamine pathway. Compound 48/80-induced shock increases histamine metabolism via this pathway resulting in mobilization of myocardial carnosine and histidine to carcinine and histamine; this effect is increased by H2 receptor blockade.
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PMID:Effect of histamine antagonists on myocardial carcinine metabolism during compound 48/80-induced shock. 221 37

The present study was made on an experimental animal model of a death from anaphylaxis, in which postmortem changes in levels of histamine and 1-methylhistamine, in whole blood were measured. Instead of the usual immunological method administering compound 48/80, a degranulating agent of mast cell and the effect closely resembling the immuno-reaction, resulted in reliable death in a short time. The animals that died rapidly after the injection of compound 48/80, were found to have large increases in levels of histamine and 1-methylhistamine soon after the administration. These results were similar to the results of injecting histamine exogenously. On the other hand, the animals that died after a longer time showed no increases in levels of those amines within about 24 h, but 24 hours after death histamine levels were only increased tremendously without rise in 1-MHA levels. These phenomena closely resembled those in the control animals that were treated with overdoses of Nembutal.
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PMID:An experimental model of death from anaphylactic shock with compound 48/80 and postmortem changes in levels of histamine in blood. 233 30

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.
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PMID:Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. 247 89

The precise roles of carnosine and histamine in the physiologic response of the cardiovascular system to stress are unknown. We have previously shown in skeletal and cardiac muscle that carnosine serves as a histidine reservoir available for subsequent histamine synthesis following trauma and sepsis. This study was designed to quantify the effect of histamine-releasing and blocking agents on the myocardial carnosine-histamine pathway as well as on survival during severe stress. Four groups of mature (9-month-old) Sprague-Dawley rats were treated with either (1) saline, (2) lodoxamide (L, mast cell degranulation inhibitor), (3) compound 48/80 (a mast cell degranulator which causes stress), or (4) L followed by 48/80, and observed until agonal or the end of 30 min. When either endpoint was reached the animals were sacrificed and their hearts were removed for tissue analyses of histidine, histamine, 3-methylhistamine, and carnosine via high-pressure liquid chromatography. All five L-pretreated animals survived challenge with 48/80 while all five animals given 48/80 alone died (P less than .005). This mortality correlated well with the increase in the myocardial levels of histidine (P less than or equal to .0005), histamine (P less than or equal to .0077), and 3-methylhistamine (P less than or equal to .0004) and the decrease in carnosine (P less than or equal to .009) experienced by the animals treated with 48/80 alone in comparison to the control, L-only- and L + 48/80-treated groups. A protective effect of L was shown against the deleterious effects of 48/80 which is associated with prevention of myocardial carnosine mobilization to histidine and histamine. These data support the role of carnosine as a nontoxic myocardial histidine reservoir which is mobilized in response to stress-induced increases in histamine requirements.
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PMID:Improved survival from compound 48/80-induced lethal stress and inhibition of myocardial histamine and carnosine mobilization by lodoxamide. 270 50

Mast cells isolated from the peritoneal fluid of Wistar rats were purified by centrifugation on Percoll gradient with a yield of 2x10(6) cells/ml. Cell morphology was well preserved as shown by light and electron microscopy. The mast cells capacity to bind histamine was assayed using either [3H]-histamine or histamine-ferritin conjugate as electron-opaque probe for electron microscopic examination. The [3H]-histamine binding performed at 4 degrees C in Ca2+-free phosphate-buffered saline pH 7.3 completed within 30 min was found to be specific, with an IC50 value of 0.72 +/- 0.23 nM. The data analyses by Scatchard and Hill's representations showed a KD of 0.60 +/- 0.24 nM and Bmax of 4.9 +/- 1.2 pM/10(6) cells suggesting that on mast cells the histamine receptors are restricted to the plasma membrane. According to Hill's analysis neither positive nor negative cooperativity (n = 1.06) appeared to be involved in the specific histamine-receptor binding. Competition experiments with 4-methylhistamine and SK&F 93479, revealed that mast cells express H2-histamine receptors. At electron microscopic level, the histamine-ferritin conjugate interstitially injected in the hamster cheek pouch was localized on the mast cell membrane.
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PMID:Histamine receptor on mast cells. 325 80

The mast cell mediator, histamine, induces a rapid and transient increase in chloride secretion across monolayers of the human colonic epithelial cell line, T84. Threshold stimulation occurred at 3 X 10(-6) M histamine and a maximal effect at 10(-4) M. The effect was reproduced by the H1 agonists 2-methylhistamine and 2-pyridylethylamine, but not by the H2 agonists 4-methylhistamine and dimaprit, suggesting the involvement of an H1 receptor. Additionally, histamine's action was inhibited by an H1 antagonist, diphenhydramine, but not by an H2 antagonist, cimetidine. Histamine treatment increased free cytosolic calcium levels, but not those of adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism of chloride secretion induced by histamine resembled that of carbachol, in that both 1) were associated with an increase in free cytosolic calcium, 2) had a site of activation at a basolaterally localized K+ channel, and 3) were potentiated by both cAMP- and cGMP-mediated secretagogues. These results suggest that histamine may act as an intestinal secretagogue via direct interactions with epithelial cells.
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PMID:Immune-related intestinal Cl- secretion. I. Effect of histamine on the T84 cell line. 333 21

Immunological functions were studied in 22 patients with mastocytosis. Lymphocyte stimulation with concanavalin A (Con A) and phytohemagglutinin showed that the patients responded with lower mitogenic activity than healthy controls. Furthermore, the lymphocytes of patients with the most extensive mast cell disease had a significantly lower Con A mitogen response than the lymphocytes of the rest of the patients. The effect of histamine and its specific metabolites, tele-methylhistamine and tele-methylimidazoleacetic acid (MeImAA), on the Con A lymphocyte mitogen response was also studied in healthy controls. Histamine had a clear suppressive effect, while the metabolite tele-methylhistamine caused only slight inhibition and MeImAA apparently had no effect. The total T cell, suppressor and helper cell numbers, measured with monoclonal antibodies, and the amount of immunoglobulins in serum were found to be normal.
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PMID:Suppression of T lymphocyte mitogen response in patients with mastocytosis. 387 30

The submandibular gland of the cat contains the typical mast cells. In these cells most of the tissue histamine is stored, and the non-mast histamine adds only a smaller part (10%) of the total histamine content in the gland. However, the stimulation of the gland (nerve stimulation, i.a. application of pilocarpine or compound 48/80) increases the non-mast cell histamine as calculated from the correlation between histamine and mast cell contents of the gland. The free histamine is taken up by different tissues of the cat and its methylated metabolite, N tau-methylhistamine, is formed. The cholinergic stimulation of the tissues causes a decrease of methylation of histamine indicating a decrease of the uptake of the amine into the cells.
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PMID:The non-mast cell histamine in the submandibular gland of the cat. 401 9


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