Mast cell antigen-induced histamine release

Figure 2. Concentration-response relationship for Ca and antigen-induced histamine release from rat mast cells (39)...

Bach, M. K., and Brashler, J. R., 1973, On the nature of the presumed receptor for IgE on mast cells. I. The effect of sialidase and phospholipase C treatment on the capacity of rat peritoneal cells to participate in IgE-mediated, antigen-induced histamine release in vitro, J. Immunol. 110 1599-1608. 

The route of antigen administration can alter the speed of antigen access to the circulation and, thus, the systemic symptoms in anaphylaxis models. For example, allergen ingestion typically induces anaphylaxis that includes gastrointestinal symptoms, such as diarrhea [4]. These intestinal anaphylaxis models in mice are dependent on IgE-induced mast cell activation, and the release of PAF and serotonin (rather than histamine) [1,4]. 

Cromoglicate inhibits mast-ceU degranulation and histamine release induced by phosphohpase A2, but does not interfere with the interaction of antigen and reaginic antibodies. Evidence is accumulating that it has an important stabilizing action on leukocytes, apart from mast cells, such as neutrophils, eosinophils, and monocytes, and that it also affects nerve reflexes in the lung (2). 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

The mast cell stabilizers currently for ophthalmic use are nedocromil and pemirolast. These drugp are used for the prevention of eye itching caused by allergic conjunctivitis. The mast cell stabilizers act by inhibiting the antigen-induced release of inflammatory mediators (eg, histamine) from human mast cells. 

Mechanism of Action An antiasthmatic and antiallergic agent that prevents mast cell release of histamine, leukotrienes, and slow-reacting substances of anaphylaxis by inhibiting degranulation after contact with antigens. Therapeutic Effect Helps prevent symptoms of asthma, allergic rhinitis, mastocytosis, and exercise-induced bron-chospasm. 

Histamine is released from mast cells in antigen-antibody reactions, as in anaphylaxis and allergy, which are the most widely known physiological reactions to histamine. However, these potentially fatal reactions are not caused by histamine alone. Other agents present in mast cells, such as serotonin, acetylcholine, bradykinin (a nonapeptide), and a slow-reacting substance or leukotriene (see chapter 8) also contribute. In the stomach, where histamine induces acid secretion, its release seems to be regulated by the peptide hormone pentagastrin. 

Fexofenadine inhibited antigen-induced bronchospasm and histamine release from mast cells. No anticholinergic or alpha adrenergic-receptor blocking effects were observed. Moreover, no sedative or other CNS effects were observed. Fexofenadine does not cross the blood-brain barrier. It inhibits skin wheal and flare responses produced by histamine injection. Following single and twice daily oral administration, antihistaminic effects occurred within 1 hour, achieved a maximum at 2-3 hours, and lasted a minimum of 12 hours. 

Flavonoids can affect the function of plasma membrane transport Na+- and K+-ATPase, mitochondrial ATPase, and Ca2+-ATPase. The Mg2+-ectoATPase of human leukocytes is inhibited by quercetin, which acts as a competitor of ATP binding to the enzyme. The sarcoplasmic reticulum Ca2+-ATPase of muscle is effectively inhibited by several flavonoids that were also active inhibitors of antigen-induced mast cell histamine release. 

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