Inhibition of histamine release

He SH, Xie H, Zhang XJ, Wang XJ. Inhibition of histamine release from human mast cells by natural chymase inhibitors. Acta Pharmacol Sin. 2004 25 822-826. 

The effects of histamine on body tissues and organs can be diminished in four ways inhibition of histamine synthesis, inhibition of histamine release from storage granules, blockade of histamine receptors, and physiological antagonism of histamine s effects. Of these approaches, only the inhibition of histamine synthesis has not been employed clinically. The focus of this chapter is on Hi histamine receptor antagonists it provides a brief overview of the H2 blockers and the inhibitors of histamine release. More details can be found in Chapters 39 and 40. 

The modulation of the N-type Ca2+ channels has been shown for some presynaptic receptors to be the mechanistic basis for the inhibition of Ca2+ influx [29]. In 1989 Takemura et al. [30] reported on the effective inhibition of histamine release from rat hypothalamic slices by the N-type Ca2+ -channel blocker ca-conotoxin. In addition Endou et al. [23] showed that to-conotoxin greatly potentiated the modulatory effect of (R)a-methylhistamine on cardiac adrenergic responses. Yang and Hatton [31] provided direct evidence for an H3 receptor-mediated modulation of ion permeability of neurons. They showed that in magnocellular histaminergic neurons from the rat posterior hypothalamus, H3... 

An important criterion for the identification of receptor subtypes is that they are related to distinct functional responses. Based on the functional potencies of thioperamide and of tiotidine, H3A- and H3B-receptors were suggested to be linked to H3-receptor mediated inhibition of histamine release and synthesis, respectively (West et al., 1990b). At present, not much additional evidence for this suggestion has been presented. Histamine H3-receptors inhibiting noradrenaline release in mouse brain cortex slices have been suggested to represent the H3A-receptor subtype (Schlicker et al., 1992 Schlicker et al., 1994). To our knowledge, functional responses in brain tissue related to the g-receptor have never been observed however. 

Additional in vitro effects of feverfew include inhibition of histamine release from mast cells and granular components from leukocytes inhibition of smooth muscle contraction cytotoxic effects on human tumor cell lines and antimicrobial effects against gram-positive bacteria, yeasts, and filamentous fungi. 

The Herbal Blend, composed of equal parts by weight of cinnamon bark extract (Cinnamomum zeylanicum), acerola fruit (Malpighia glabra), and Spanish needles powder (Bidens pilosa), was one of the first combination formulas assayed. Surprisingly, it showed synergistic inhibition of histamine release The sum of the inhibition of the three ingredients was 10.2% of control, whereas their combination inhibited histamine release to -52% (i.e., to below the concentration of histamine found in unstimulated cells). 

Aqueous extract of clove flower bud inhibits immediate hypersensitivity in rats by inhibition of histamine release from mast cells in vivo and in vitro (Kim et al., 1998). 

INHIBITION OF HISTAMINE RELEASE MAST CELL STABILIZERS... 

Bottinger H, Reuner KH, Aktories K (1987) Inhibition of histamine release from rat mast cells by botulinum C2 toxin. In Infernatl Archiv Allergy AppI Immun. 84 ... 

Even though various antileukotriene drugs have been synthesized, none has reached clinical acceptability. Inhibition of histamine release by an apparent mast cell stabilizing mechanism (in lung tissue, but probably not elsewhere) is achieved with the carboxy-chromone derivative cromolyn sodium. The mechanism is believed to involve inhibition of histamine release from pulmonary mast cells by blocking Ca2+ movement through membrane channels. 

It inhibits the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes and platelets. In vitro, nedocromil inhibits the release of mediators including histamine, leukotriene C4 and prostaglandin D2. Similar studies with human bronchoalveolar cells showed inhibition of histamine release from mast cells and beta-glucuronidase release from macrophages. 

In the last few years, interest in triterpenes as anti-inflammatory agents and their mechanisms of action has also increased greatly. Oleanolic acid and ursolic acid have been recognised to have anti-inflammatory activity in carrageenan-induced paw edema in rats or mice, adjuvant-induced arthritis in rats, etc. Oleanolic acid, in addition, was able to suppress the delayed hypersensitivity reaction in mice induced by dinitrochlorobenzene (DNCB). These effects are attributable to different mechanisms of action ranging from the inhibition of histamine release to inhibition of complement activity [1,58]. 

Corticosteroids can decrease inflanunatoty responses in the lung by several mechanisms.These include the inhibition of synthesis of inflammatory prostanoids, induction of P2-adrenergic receptors, and the inhibition of histamine release through stabilization of mast cells. 

Figure 8. Inhibition of histamine release induced by the Ca ionophore A23187 (0.6fM) (D by removal of glucose and addition of cyanide (CN ) or 2-deoxy-l)-glucose. Cells were preincubated with inhibitors for 30 min before addition of A231S7. The action of inhibitors on release caused by a non-Ca-dependent ionophore, XSSI A is shown for comparison ( ).

Inhibition of Calcium Movement. Figure 15 shows that cromoglycate inhibits membrane permeability to 45-calclum over the same concentration range for the inhibition of histamine release. Furthermore when cromoglycate was compared with dibutyryl cyclic AMP and doxantrazole, the relative potencies of the drugs for inhibition of histamine release (doxantrazole cromoglycate dibutyryl... 

Figure 16. Inhibition of histamine release by cromoglycate (lOitM) added to cells either mixed with, or at various intervals prior to, the stimulus to release histamine. Each point is the mean and SE mean of 4 experiments and is expressed as a percentage of the maidmum inhibition in each experiment. (Data supplied by Dr. L. G. Garland—unpublished).

Fisure 2. Kinetics of cholinergic stimulation (enhanced histamine release) at high lodoxamide concentrations (SOO/ig/mL) and inhibition of histamine release at low concentrations (Sjj /mL). Ficoll-purified mast cells were incubated for various time periods with lodoxamide followed by 48j80. The mixture was filtered over Mdl ore S-jurn filters to stop the reaction. The filter was washed with 15 mL of phosphate-buffered saline, pH 7.2. The wash and filtrate were collected and analyzed for released histamine, and the release assay was compared to total levels in acid-boiled cell mixtures. 

In Table X are shown both the inhibition of histamine release and SRS-A release from Rhesus monkey lung tissue. Our observations with this system Indicate that inhibition of both mediators does not usually follow the same dose related pattern and that frequently a compound will be more effective at inhibiting histamine release than it will be at inhibiting SRS-A release. 

I. Pharmacology. Epinephrine is an endogenous catecholamine with alpha- and beta-adrenergic agonist properties, used primarily in emergency situations to treat anaphylaxis or cardiac arrest. Beneficial effects include inhibition of histamine release from mast cells and basophils, bronchodilation, positive inotropic effects, and peripheral vasoconstriction. Epinephrine is not active after oral administration. Subcutaneous injection produces effects within 5-10 minutes, with peak effects at 20 minutes. Intravenous or inhalational administration produces much more rapid onset. Epinephrine is rapidly inactivated in the body, with an elimination half-life of 2 minutes. 

It has been suggested the local anaesthetics might have the opposite effect, namely inhibition of histamine release (Mongar and Schild 1957). This effect, if true, would to a certain extent cancel out an anaphylactic response to the drug. One of the relevant observations was that in some leucocyte experiments we noticed that histamine release was significantly lower in the presence of certain local anaesthetics, e.g., prilocaine, than in their absence (Tyrode solution was used in all experiments). 

Nakamura T, Ui M (1983) Suppression of passive cutaneous anaphylaxis by pertussis toxin, an islet-activating protein, as a result of inhibition of histamine release from mast cells. Biochem Pharmacol 32 3435-3441... 

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