Vardenafil ameliorates immunologic- and non-immunologic-induced allergic reactions

2014 ◽  
Vol 92 (3) ◽  
pp. 175-180 ◽  
Author(s):  
Mohammed S. El-Awady ◽  
Eman Said
Keyword(s):  
Mast Cell ◽  
Histamine Release ◽  
Body Mass ◽  
Protective Efficacy ◽  
Pde5 Inhibitor ◽  
Inflammatory Cells ◽  
Protective Role ◽  
Blue Dye ◽  
Allergic Reactions ◽  
Peritoneal Mast Cells

Cyclic nucleotides, such as cAMP and cGMP, play a protective role in the modulation of the activity of some inflammatory cells in allergic disorders. Their intracellular concentrations are tightly regulated by the phosphodiesterases (PDEs). The protective efficacy of the selective PDE5 inhibitor vardenafil against mast-cell-mediated allergic reactions in murine models has been investigated. Compound 48/80 was used as a direct mast cell degranulator to induce anaphylaxis. Vardenafil (administered orally at 5, 10, 20, 40, and 80 mg/kg body mass) significantly (P < 0.05, n = 12) increased protection against compound-48/80-induced anaphylaxis in mice to 33.33%, 66.67%, 66.67%, 83.33%, and 66.67% respectively compared with the control (vehicle). In passive cutaneous anaphylaxis (PCA) in rats, vardenafil (10 mg/kg body mass) significantly (P < 0.05, n = 6) decreased Evans’ blue dye extravasation (4.6-fold). Pre-incubation of isolated rat peritoneal mast cells (RPMCs) with vardenafil (10 and 100 μmol/L) significantly (P < 0.05, n = 6) reduced compound-48/80-induced histamine release by 2.8- and 3-fold, respectively. Moreover, histamine release by immunogenic stimulation of sensitized RPMCs by egg albumin significantly declined following pre-incubation with vardenafil (10 and 100 μmol/L) by 1.94- and 1.99-fold, respectively. In conclusion, inhibition of PDE5 by vardenafil ameliorated immunologic and non-immunologic mast-cell-mediated allergic reactions and reduced histamine release, providing evidence for the potential anti-allergic properties of vardenafil.

Comparison of intestinal mast cell and basophil histamine release in children with food allergic reactions

Allergy ◽  
1989 ◽  
Vol 44 (8) ◽  
pp. 554-565 ◽  
Author(s):  
H. NOLTE ◽  
P. O. SCHIØTZ ◽  
A. KRUSE ◽  
P. STAHL SKOV
Keyword(s):  
Mast Cell ◽  
Histamine Release ◽  
Allergic Reactions

Inhibitory Effects of BiRyuChe-Bang on Mast Cell-Mediated Allergic Reactions and Inflammatory Cytokines Production

2013 ◽  
Vol 41 (06) ◽  
pp. 1267-1282 ◽  
Author(s):  
Phil-Dong Moon ◽  
Il Sang Choi ◽  
Ji-Hyun Go ◽  
Byong-Joo Lee ◽  
Sang Woo Kang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Inflammatory Cytokines ◽  
Medical Center ◽  
Human Mast Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Allergic Reactions ◽  
Linalyl Acetate ◽  
Tnf Α

BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells.

scholarly journals Anti-immunoglobulin-induced histamine secretion by rat peritoneal mast cells studied by immunoferritin electron microscopy.

1975 ◽  
Vol 142 (2) ◽  
pp. 391-402 ◽  
Author(s):  
D Lawson ◽  
C Fewtrell ◽  
B Gomperts ◽  
M Raff
Keyword(s):  
Electron Microscopy ◽  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Histamine Secretion ◽  
Calcium Dependent ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

We have used ferritin-conjugated divalent and monovalent anti-Ig antibodies to study simultaneously, histamine secretion and the ultrastructural distribution and redistribution of Ig receptors on rat peritoneal mast cells. We conclude that (a) divalent anti-Ig is required for both receptor redistribution and for calcium-dependent degranulation and histamine release, (b) divalent anti-Ig induces patching and pinocytosis but not capping of Ig molecules, (c) neither capping nor pinocytosis are required for triggering and if clustering is necessary, then less than 10 Ig molecules are required per cluster, and (d) degranulation (and histamine release) is not an all or none response of the mast cell.

scholarly journals ANTIGEN-INDUCED RELEASE OF SLOW REACTING SUBSTANCE OF ANAPHYLAXIS (SRS-ARAT) IN RATS PREPARED WITH HOMOLOGOUS ANTIBODY

1968 ◽  
Vol 127 (4) ◽  
pp. 767-782 ◽  
Author(s):  
Robert P. Orange ◽  
Martin D. Valentine ◽  
K. Frank Austen
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Reaction Sequence ◽  
Peritoneal Mast Cells ◽  
Pmn Leukocytes ◽  
Circulating Lymphocytes ◽  
Pharmacologic Inhibitors ◽  
Antigen Antibody ◽  
Marked Suppression

The polymorphonuclear leukocyte appears to be an essential cellular prerequisite for the antigen-induced release of SRS-Arat in the peritoneal cavity of rats prepared with homologous, hyperimmune antisera. Depletion of PMN leukocytes is associated with a marked suppression of SRS-Arat release, whereas depletion of circulating lymphocytes or peritoneal mast cells does not influence the antigen-induced release of SRS-Arat. A local increase in the number of PMN leukocytes produced by the induction of a peritoneal exudate was associated with an enhanced release of SRS-Arat. A distinct difference in the cellular requirements for the antigen-induced release of histamine and SRS-Arat in the rat was observed. Homocytotropic antibody-mediated histamine release could be achieved in leukopenic rats but not in mast cell-depleted animals. Conversely, SRS-Arat release was suppressed in leukopenic rats but was unaffected by mast cell depletion. Diethylcarbamazine inhibited the antigen-induced release of SRS-Arat following preparation with homologous, hyperimmune antisera but did not interfere with homocytotropic antibody-mediated histamine release. In preventing SRS-Arat release, diethylcarbamazine did not interfere with antigen-antibody interaction since desensitization of tissues was possible in the presence of this inhibitor. This observation is consistent with the view that diethylcarbamazine inhibits the reaction sequence leading to the formation and release of SRS-Arat at some step subsequent to antigen-antibody interaction. These studies support the view that the immunologic pathways leading to the release of SRS-Arat and histamine in the rat are distinctly different in terms of the immunoglobulins involved, the cellular prerequisites, and the effective pharmacologic inhibitors.

Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells

2009 ◽  
Vol 87 (8) ◽  
pp. 624-632 ◽  
Author(s):  
Chi-Kong Yeung ◽  
Jessica Ka-Yan Law ◽  
Sze-Wing Sam ◽  
Sven Ingebrandt ◽  
Hang-Yung Alaster Lau ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Potassium Channel ◽  
Histamine Release ◽  
Field Potential ◽  
Peritoneal Mast Cell ◽  
Induced Response ◽  
Potassium Channel Openers ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

To determine whether changes in membrane potential affect the extent of mast cell degranulation, compound 48/80 was added to rat peritoneal mast cell suspensions in the absence or presence of potassium channel openers (KCOs). Changes were compared between the field potential (FP) and the amount of histamine released. The results demonstrated that (i) the onset and duration of FP, which reflects the hyperpolarizing nature of the response, increased as the concentration of compound 48/80 increased; (ii) both FP and the amount of histamine released increased as the concentration of compound 48/80 increased; (iii) although both KCOs (SDZ PCO400, a benzopyran derivative, and P1060, a cyanoguanidine derivative) potentiated compound 48/80-induced increases in FP and histamine release, without compound 48/80, they had no effect on either parameter; (iv) both glibenclamide and charybdotoxin significantly attenuated the compound 48/80-induced increase in FP; and (v) glibenclamide was able to attenuate the KCO-induced potentiation of FP. The results show that drugs presumably causing hyperpolarization can affect histamine release from rat peritoneal mast cells. The effect of KCOs on compound 48/80-induced response appears to be potentiation in nature rather than synergism. It is possible that KCO hyperpolarizes the cell membrane, enhances Ca2+ influx, and thus increases histamine release. As such, selective blockers of K+ channels may be useful for the treatment of immunological disorders.

Amomum xanthiodes Inhibits Mast Cell-Mediated Allergic Reactions Through the Inhibition of Histamine Release and Inflammatory Cytokine Production

2005 ◽  
Vol 230 (9) ◽  
pp. 681-687 ◽  
Author(s):  
Sang-Hyun Kim ◽  
Tae-Yong Shin
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Proinflammatory Cytokines ◽  
Immunoglobulin E ◽  
Ionophore A23187 ◽  
Allergic Reactions ◽  
Disodium Cromoglycate ◽  
Plasma Histamine ◽  
Intracellular Ca

In this study, we investigated the effect of Amomum xanthiodes (Zingiberaceae) extract (AXE) on the mast cell-mediated allergy model and studied the possible mechanism of action. We found that AXE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. Additionally, AXE decreased immunoglobulin E (IgE)-mediated local allergic reactions and passive cutaneous anaphylaxis (PCA), and AXE dose-dependently attenuated the release of histamine from rat peritoneal mast cells (RPMC) activated by compound 48/80 or IgE. The amounts of AXE needed for inhibition of compound 48/80-induced plasma histamine release and PCA were similar to disodium cromoglycate, the known anti-allergic drug. We found that AXE increased the cAMP levels and decreased the compound 48/80-induced intracellular Ca2+. Furthermore, AXE attenuated the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187)-stimulated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 secretion in human mast cells. The inhibitory effect of AXE on the proinflammatory cytokines was nuclear factor-κB (NF-κB)-dependent. In addition, AXE decreased PMA plus A23187-induced degradation of IκBα and the nuclear translocation of NF-κB. Our findings provide evidence that AXE inhibits mast cell-derived immediate-type allergic reactions, and that cAMP, intracellular Ca2+, proinflammatory cytokines, and NF-κB are involved in these effects.

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