Inhibition of Allergen-Mediated Histamine Release from Human Cells by Ketotifen and Oxatomide

Radermecker, Maurice

doi:10.1159/000194358

Cited by 25 publications

(9 citation statements)

References 12 publications

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“…Since the description by Church and Gradidge [12]and Radermecker [13]in the early eighties of the anti–histamine–releasing properties of oxatomide and ketotifen, all the second–generation H 1 –antihistamines were tested in vitro for their ability to block the release of mediators from mast cells and basophils.…”

Section: The Inhibition Of Mediator Releasementioning

confidence: 99%

Hypothetical Mechanisms of Action of an H1–Antihistamine in Asthma

Rihoux

Michel²,

Arnold³

et al. 1999

Int Arch Allergy Immunol

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Some recent clinical studies carried out with the potent H₁–antihistamine cetirizine (CTZ) suggest that this drug could be useful for the treatment of mild to moderate asthma and even for the prevention of the disease. Besides a potent antagonism of H₁–receptors at bronchial level, this drug was also shown to exert a large series of anti–inflammatory effects in in vitro, ex vivo and in vivo pharmacological models and also in clinical situations in atopic subjects. All the data collected up to now suggest the possible existence in the molecule of a central key mechanism of action on resident cells especially involved in cell trafficking and bronchial inflammation, i.e a down–regulating effect on the nuclear factor_KB (NF_KB). This hypothesis was tested on human endothelial cells and a human epithelial pulmonary cell line using different experimental methods. The results showed that CTZ down–regulates the TNF–α–induced hyperactivation of NF_KB in these two different resident cells at physiological concentrations.

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Section: The Inhibition Of Mediator Releasementioning

confidence: 99%

Hypothetical Mechanisms of Action of an H1–Antihistamine in Asthma

Rihoux

Michel²,

Arnold³

et al. 1999

Int Arch Allergy Immunol

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“…Ketotifen also inhibits the release of histamine and slow-reacting substance of anaphylaxis (SRS-A) leukotrienes from peripheral human leukocytes induced by both immunogenic (anti-IgE) and non-immunogenic (cal cium ionophore A23187) stimuli [31][32][33]. When examined in human chopped lung [25,34], ketotifen shows poor inhi bition of histamine release but a significant reduction in the generation and release of SRS-A leukotrienes.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Modulatory Effect of Ketotifen, Sodium Cromoglycate, Procaterol and Salbutamol in Human Skin, Lung and Tonsil Mast Cells

Okayama

Church

1992

Int Arch Allergy Immunol

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To assess the influence of mast cell heterogeneity on the inhibition of mediator release by drugs, the effects of ketotifen, sodium cromoglycate and β-adrenoceptor agonists were examined against IgE-dependent histamine and prostaglandin D₂ release from enzymatically dispersed human skin, lung and tonsil-lar mast cells. At high concentrations, ketotifen was an inhibitor of histamine and prostaglandin D₂ release from lung and tonsillar mast cells. No cross-tachyphylaxis with sodium cromoglycate was seen. In skin mast cells no inhibition of mediator release was observed with 1.0 μM ketotifen, above which histamine release was induced. Sodium cromoglycate was a weak inhibitor of histamine and prostaglandin D₂ release from lung and tonsillar mast cells and showed tachyphylaxis. Sodium cromoglycate did not inhibit histamine and prostaglandin D₂ release from skin mast cells. On the other hand, no heterogeneity was observed with the β-adrenoceptor agonists, procaterol and salbutamol. β-Adrenoceptor stimulants were significantly more effective in inhibiting prostaglandin D₂ than histamine release. No tachyphylaxis was seen with prolongation of the incubation time before challenge. Our results suggest that human mast cells are heterogeneous with respect to the modulation of mediator release by ketotifen and sodium cromoglycate but not β-adrenoceptor agonists.

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“…Ketotifen is a pharmacological agent that has been reported to suppress IgE-or compound 48/80-evoked release of histamine from mast cells, but it also acts as an antagonist at the histamine H 1 receptor (11,22,45). Presence of 100 M ketotifen in the incubation medium did not suppress 5-HTevoked release of histamine from guinea pig or human preparations (data not shown).…”

Section: Ketotifenmentioning

confidence: 89%

Mast cell expression of the serotonin_1Areceptor in guinea pig and human intestine

Wang

Zou

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature. enteric mast cells; histamine; enteric nervous system; functional gastrointestinal disorders; irritable bowel syndrome MAST CELLS ARE PRESENT in continuously varying numbers in the intestinal mucosa, lamina propria, and smooth muscle coats. Mast cell numbers expand in parasitic nematode infections and are major factors associated with inflammation-related changes in Clostridium difficile and other bacterial infections (5, 52). Increased numbers of enteric mast cells are associated with inflammatory responses in general (e.g., radiation-induced inflammation) (36). In humans, numbers of enteric mast cells are elevated in diarrhea-predominant irritable bowel syndrome (D-IBS) relative to healthy controls (1,9,40,41). Moreover, elevated mast cell numbers contribute to release of greater amounts of the preformed mast cell mediator histamine from mucosal biopsies removed from patients with postinfectious D-IBS (1). Increased concentrations of histamine in the incubation medium, in these cases, evoke higher frequencies of firing of secretomotor neurons when applied to preparations from the submucosal plexus of guinea pigs in vitro (6, 7).Enteric mast cells release two kinds of mediators (44). Preformed mediators are stored in cytoplasmic granules and released when the mast cells discharge the granules into the extracellular environment. Examples of preformed mediators are histamine and serine ...

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Inhibition of Allergen-Mediated Histamine Release from Human Cells by Ketotifen and Oxatomide

Cited by 25 publications

References 12 publications

Hypothetical Mechanisms of Action of an H1–Antihistamine in Asthma

Hypothetical Mechanisms of Action of an H1–Antihistamine in Asthma

Comparison of the Modulatory Effect of Ketotifen, Sodium Cromoglycate, Procaterol and Salbutamol in Human Skin, Lung and Tonsil Mast Cells

Mast cell expression of the serotonin_1Areceptor in guinea pig and human intestine

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Inhibition of Allergen-Mediated Histamine Release from Human Cells by Ketotifen and Oxatomide

Cited by 25 publications

References 12 publications

Hypothetical Mechanisms of Action of an H1–Antihistamine in Asthma

Hypothetical Mechanisms of Action of an H1–Antihistamine in Asthma

Comparison of the Modulatory Effect of Ketotifen, Sodium Cromoglycate, Procaterol and Salbutamol in Human Skin, Lung and Tonsil Mast Cells

Mast cell expression of the serotonin1Areceptor in guinea pig and human intestine

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Mast cell expression of the serotonin_1Areceptor in guinea pig and human intestine