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)

In addition to the autonomic nervous system and gut hormones, the mast cell mediator histamine has also been associated with exocrine pancreatic secretion. This review is concerned with the distribution and the physiological role of histamine in the control of pancreatic juice secretion. Histamine is distributed widely around blood vessels and acinar tissues in the pancreas and it is released in pancreatic juice during secretagogue stimulation. Histamine has a marked secretagogue effect in the exocrine pancreas of several animal species but in many cases the secretory effect is gender-related. The paracrine hormone exerts its secretory response via activation of H1 and H2 receptors on pancreatic acinar cells to mobilize potassium ions (K+) and cellular calcium (Ca2+) and through elevation of endogenous adenosine 3',5' cyclic monophosphate (cyclic AMP) levels, respectively. A physiological role for H3 receptors has also been associated with exocrine pancreatic secretion. H3 receptors are located presynaptically on parasympathetic nerve terminals to control the release of acetylcholine via restriction of Ca2+ access into nerve terminal through the N-type Ca2+ channel. Taken together, the results presented in this review strongly support histamine as a potential modulator of exocrine pancreatic function.
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PMID:The physiological role of histamine in the exocrine pancreas. 919 85

We investigated the mechanism by which inosine, a metabolite of adenosine that accumulates to > 1 mM levels in ischemic tissues, triggers mast cell degranulation. Inosine was found to do the following: (a) compete for [125I]N6-aminobenzyladenosine binding to recombinant rat A3 adenosine receptors (A3AR) with an IC50 of 25+/-6 microM; (b) not bind to A1 or A2A ARs; (c) bind to newly identified A3ARs in guinea pig lung (IC50 = 15+/-4 microM); (d) lower cyclic AMP in HEK-293 cells expressing rat A3ARs (ED50 = 12+/-5 microM); (e) stimulate RBL-2H3 rat mast-like cell degranulation (ED50 = 2.3+/-0.9 microM); and (f) cause mast cell-dependent constriction of hamster cheek pouch arterioles that is attenuated by A3AR blockade. Inosine differs from adenosine in not activating A2AARs that dilate vascular smooth muscle and inhibit mast cell degranulation. The A3 selectivity of inosine may explain why it elicits a monophasic arteriolar constrictor response distinct from the multiphasic dilator/constrictor response to adenosine. Nucleoside accumulation and an increase in the ratio of inosine to adenosine may provide a physiologic stimulus for mast cell degranulation in ischemic or inflamed tissues.
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PMID:Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation. 938 51

Characterization of A2B receptors is hampered by the lack of selective pharmacological probes and often relies on their relative affinity to agonists that are selective at other receptor types. This approach is limited because the affinity of A2B receptors for putative A3 agonists has not been determined. Using the human erythroleukemia cell line HEL as a cellular model for A2B-mediated adenylate cyclase activation, we found the following potencies (pD2) for the non-selective agonist 5'-N-ethylcarboxamidoadenosine (NECA) (5.65 +/- 0.04), the putative A3 agonists N6-benzyl-NECA (4.17 +/- 0.06) and N6-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (IB-MECA) (3.7 +/- 0.02), and the A2A agonist 4-[(N-ethyl-5'-carbamoyladenos-2-yl)-aminoethyl]-phenylpropionic acid (CGS21680) (2.8 +/- 0.1). Because of the lack of a selective agonist, characterization of A2B receptor function is difficult in cells co-expressing A2A receptors. In the human mast cell line HMC-1, NECA induced cAMP accumulation with a concentration-response relationship best fitted to a two-sited model (pD2 7.69 +/- 0.42 and 5.92 +/- 0.21 for high- and low-affinity sites), suggesting the presence of both A2A and A2B receptors in these cells. We demonstrated that A2B receptors can be selectively activated with NECA in the presence of the selective A2A antagonist 5-amino-7-(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c ]pyrimidine (SCH 58261). Under these conditions, the concentration-response relationship of NECA for cyclic AMP accumulation was now best fitted to a one-site model (pD2 5.68 +/- 0.03, Hill slope 0.93 +/- 0.06, 95% confidence intervals 0.8 to 1.06) corresponding to selective activation of A2B receptors. Using the approaches developed in this study, we determined that A2B, and not A2A or A3, receptors account for all the calcium mobilization induced by NECA in HMC-1 cells.
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PMID:Pharmacological characterization of adenosine A2B receptors: studies in human mast cells co-expressing A2A and A2B adenosine receptor subtypes. 951 73

We investigated the effect of spirulina on mast cell-mediated immediate-type allergic reactions. Spirulina dose-dependently inhibited the systemic allergic reaction induced by compound 48/80 in rats. Spirulina inhibited compound 48/80-induced allergic reaction 100% with doses of 100-1000 microg/g body weight, i.p. Spirulina (10-1000 microg/g body weight, i.p.) also significantly inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. When rats were pretreated with spirulina at a concentration ranging from 0.01 to 1000 microg/g body weight, i.p., the serum histamine levels were reduced in a dose-dependent manner. Spirulina (0.001 to 10 microg/mL) dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, when spirulina (10 microg/mL) was added, transiently and significantly increased about 70-fold at 10 sec compared with that of control cells. Moreover, spirulina (10 microg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results indicate that spirulina inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.
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PMID:Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by spirulina. 960 30

We have examined the effect of succinic acid on anaphylaxis. Succinic acid (100 mM) significantly inhibited systemic anaphylaxis induced by compound 48/80 in mice and dose-dependently inhibited local anaphylaxis activated by anti-dinitrophenyl IgE. Further 10 and 100 mM significantly inhibited histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-dinitrophenyl IgE. In addition succinic acid (0.1 and 1 mM) had a significant inhibitory effect on anti-dinitrophenyl IgE-induced tumour necrosis factor-alpha secretion from rat peritoneal mast cells. The level of cyclic AMP in rat peritoneal mast cells, when succinic acid (100 mM) was added, transiently and significantly increased about 4 times compared with that of basal cells. These results suggest a possible use of succinic acid in managing mast cell-dependent anaphylaxis.
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PMID:Inhibition of mast cell-dependent anaphylaxis by succinic acid. 1022 65

Sodium salicylate (NaSal) is a commonly used agent with a wide pharmacological spectrum. The objective of the present study was to investigate the effect of NaSal on anaphylaxis. NaSal (10-1 and 1 mm) significantly inhibited systemic anaphylaxis induced by compound 48/80 in rats. NaSal also significantly inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) immunoglobulin E (IgE). NaSal (10-1 and 1 mm) significantly inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Northern-blot analysis demonstrated that a significantly reduced level of the mRNA of L-histidine decarboxylase was expressed in mast cells treated with NaSal, compared with that without NaSal. NaSal (10-2 and 10-1 mm) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha secretion from RPMC. The level of cyclic AMP in RPMC, when NaSal (1 mm) was added, transiently and significantly increased about sixfold compared with that of basal cells. These results suggest a possible use of NaSal in managing mast cell-dependent anaphylaxis.
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PMID:Inhibition of mast cell-dependent anaphylaxis by sodium salicylate. 1023 41

Activation of mast cells by aggregation of their IgE receptors induces rapid and transient synthesis of cyclooxygenase-2 (COX-2). In this study we investigated (i) the cis-acting response elements and transcription factors active at the COX-2 promoter and (ii) the signal transduction pathways mediating COX-2 induction following aggregation of mast cell IgE receptors. Transient transfection assays with COX-2 promoter/luciferase constructs suggest that a consensus cyclic AMP response element is essential for induced COX-2 expression. Cotransfection studies with plasmids expressing c-Jun, dominant negative Ras, dominant negative c-Jun NH(2)-terminal kinase, and dominant negative MEKK1 demonstrate that activation of the Ras/MEKK1/c-Jun NH(2)-terminal kinase/c-Jun pathway is required for COX-2 promoter-mediated luciferase expression. Attenuation of COX-2 promoter activity by dominant negative constructs for Raf-1, ERK1, and ERK2 suggests that the Ras/Raf-1/extracellular signal-regulated kinase pathway is also necessary for COX-2 induction. Although mutating the two NF-IL6 sites individually did not affect COX-2 promoter activity, mutating both NF-IL6 sites substantially inhibits COX-2 promoter activity. Moreover, overexpression of wild type CCAAT/enhancer-binding protein-beta (C/EBPbeta) augments COX-2 promoter activity in activated mast cells and cotransfection of a dominant negative C/EBPbeta construct completely blocks COX-2 promoter/luciferase expression. Our data suggest that in activated mast cells, a Ras/MEKK1/c-Jun NH(2)-terminal kinase signal transduction pathway activating c-Jun, a Ras/Raf-1/extracellular signal-regulated kinase pathway, and activated C/EBPbeta facilitate COX-2 induction via the cyclic AMP response element and NF-IL6 sites of the COX-2 promoter.
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PMID:Transcriptional regulation of the cyclooxygenase-2 gene in activated mast cells. 1065 93

We investigated the effect of aqueous extract of Perilla frutescens (Labiatae) (PFAE) on the mast cell-mediated immediate-type allergic reactions. PFAE (0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in rats. PFAE (0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. When PFAE was pretreated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. PFAE (10(-3) to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When PFAE (1 mg/ml) was added, transiently and significantly increased about 4-fold compared with that of basal cells. Moreover, PFAE (0.001 and 0.01 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results indicate that PFAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.
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PMID:Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens. 1094 27

We investigated the effect of aqueous extract of Gleditsia sinensis thorns (Leguminosae) (GSAE) on the mast cell-dependent anaphylaxis. GSAE (0.005 to 1 g/kg) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. GSAE (0.1 and 1 g/kg) also significantly inhibited local anaphylaxis activated by anti-DNP IgE. When GSAE was pretreated at the same concentrations with systemic anaphylaxis, the plasma histamine levels were reduced in a dose-dependent manner. GSAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When CSAE (1 mg/ml) was added, transiently and significantly increased about fourfold compared with that of basal cells. Moreover, GSAE (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results suggest a possible use of GSAE in managing mast cell-dependent anaphylaxis.
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PMID:Inhibitory effect of mast cell-dependent anaphylaxis by Gleditsia sinensis. 1097 91

The antiasthmatic drug enprofylline was the first known selective, though not potent, A(2B) antagonist. On the basis of structure-activity relationships (SARs) of xanthine derivatives, we designed a novel selective adenosine A(2B) receptor antagonist, 3-isobutyl-8-pyrrolidinoxanthine (IPDX), with potency greater than that of enprofylline. IPDX displaced [3H]ZM241385 ([3H]4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a]-[1,3,5]triazin-5-ylamino]ethyl)phenol) from human A(2B) adenosine receptors with a K(i) value of 470 +/- 2 nM and inhibited A(2B)-dependent cyclic AMP (cAMP) accumulation in human erythroleukemia (HEL) cells with a K(B) value of 625 +/- 71 nM. We found that IPDX was more selective than enprofylline toward human A(2B) receptors. It was 38-, 55-, and 82-fold more selective for human A(2B) than for human A(1) (K(i) value of 24 +/- 8 microM), human A(2A) (K(B) value of 36 +/- 8 microM), and human A(3) (K(i) value of 53 +/- 10 microM) adenosine receptors, respectively. IPDX inhibited NECA (5'-N-ethylcarboxamidoadenosine)-induced interleukin-8 secretion in human mast cells (HMC-1) with a potency close to that determined for A(2B)-mediated cAMP accumulation in HEL cells, thus confirming the role of A(2B) adenosine receptors in mediating human mast cell activation. Since adenosine triggers bronchoconstriction in asthmatic patients through human mast cell activation, IPDX may become a basis for the development of new antiasthmatic drugs with improved properties compared with those of enprofylline. Our data demonstrate that IPDX can be used as a tool to differentiate between A(2B) and other adenosine receptor-mediated responses.
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PMID:Inhibition of human mast cell activation with the novel selective adenosine A(2B) receptor antagonist 3-isobutyl-8-pyrrolidinoxanthine (IPDX)(2). 1170 49


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