Inhibition Of Anaphylactic Histamine Release Research Articles

L-Ephedrine is a major constituent of Mao-Bushi-Saishin-To, one of the formulas of Chinese medicine, which shows immediate inhibition after oral administration of passive cutaneous anaphylaxis in rats.

Whether Mao-Bushi-Saishin-To (MBST), one of the formulas of classical Chinese medicine, is effective on 48-h passive cutaneous anaphylaxis (PCA) in rats and which substance in the formula is responsible for its inhibitory action were examined. In the studies on PCA, MBST (hot water extract of the whole herbal formula), extracts of Ephedra herb (Mao), l-ephedrine and other reference drugs were orally administered immediately or at various times before or 5 min after the antigen challenge. In the experiments on anaphylactic histamine release from rat peritoneal mast cells, l-ephedrine and d-pseudoephedrine were added at 10(-4)-10(-7) g/ml at 30, 10, 3 or 0 min before antigen provocation. The time course study indicated that MBST produced a prompt and long lasting inhibition of PCA. Among the constituents of Mao, l-ephedrine exerted this prompt inhibitory activity, but d-pseudoephedrine did not. Neither pseudoephedrine nor l-ephedrine prevented the anaphylactic histamine release from isolated peritoneal mast cells. It is strongly emphasised that the rapid suppression of PCA by orally administered l-ephedrine must be exerted by a mechanism distinct from that of suppression produced following gastrointestinal absorption of the drug, because the time required for the inhibition was extraordinarily short. However, direct inhibition of anaphylactic histamine release from isolated mast cells was excluded in this inhibition of PCA.

Involvement of β-Adrenergic Systems in the Antagonizing Effect of Paeoniflorin on the Scopolamine-Induced Deficit in Radial Maze Performance in Rats

Whether anaphylactic histamine release from rat peritoneal mast cells is influenced by betahistine, a histamine H1-receptor agonist/H3-antagonist, and dimaprit, an H2-agonist, was examined. Treatment with dimaprit at 6 and 60 microM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 microM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 microM for 1 to 20 min and for 5 to 20 min, respectively, caused a time-dependent inhibition of the release, but up to 30 min treatment with 8 and 80 microM betahistine had no effect. The decreased histamine release induced by dimaprit was recovered by neither mepyramine nor cimetidine. However, thioperamide, an H3-selective antagonist, dose-dependently restored the diminished release. From these results, the inhibition of anaphylactic histamine release by dimaprit is not produced by the stimulation of H2-receptors, but involves the stimulation of H3-like receptors or H3-subtype receptors, which are distinct from the H3-receptors located in brain, and suggests that the receptor plays an important role in the negative feedback regulation of histamine release.

Effect of TMB-8 on calcium transport in mast cells in relation to histamine secretion

We have previously reported an inhibition of histamine release by TMB-8 both in the presence and absence of calcium and with glucose in the medium. In the present investigation we have studied the effect of TMB-8 on calcium transport. The observations show that TMB-8 inhibits calcium uptake and enhances calcium efflux in mast cells. As antigen-induced histamine release from sensitized mast cells is primarily dependent on extracellular calcium, the inhibition of anaphylactic histamine release by TMB-8 is probably mainly due to an inhibition of calcium influx into the mast cells. We have shown an increased calcium efflux during histamine release from mast cells induced by compound 48/80 in the absence of calcium in the medium, suggesting the release of intracellular calcium stores. The increased calcium efflux was not inhibited by TMB-8. On the contrary, the enhanced calcium efflux caused by compound 48/80, was added to that by TMB-8. TMB-8 thus had no effect on the calcium release from intracellular stores by compound 48/80 but the enhanced calcium efflux by TMB-8 would tend to inhibit histamine release.

Calcium uptake in mast cells, energy metabolism and histamine secretion

The inhibition of energy metabolism of mast cells causes an inhibition of histamine secretion. As the secretion is generally initiated by the influx of calcium into the cell, we have made correlative studies of the effect of blocking the energy metabolism on calcium uptake and histamine secretion. When the influx of calcium is increased by exposing the cells to low concentrations of saponin or ionophore A23187, histamine release occurs, having the character of a secretory response. Brief incubation of the cells with antimycin A, 10(-9) M-10(-7) M, prior to exposure to saponin or the calcium ionophore gave similar dose-response curves for the inhibitory effect of antimycin A on calcium uptake and histamine release. The inhibition of calcium uptake in untreated mast cells by antimycin A, 10(-9) M-10(-7) M, showed good correlation to the inhibition of anaphylactic histamine release and the release induced by compound 48/80. The antigen-induced histamine release is dependent on extracellular calcium and an inhibition of its uptake by antimycin A could by itself inhibit the release. Compound 48/80 on the other hand induces histamine release both in the presence and absence of calcium, and both are similarly inhibited by 10(-9) M-10(-7) M antimycin A. This indicates that antimycin A has other sites of action apart from the inhibition of the influx of extracellular calcium. The inhibitory effect of antimycin A on compound 48/80-induced histamine secretion in the absence of extracellular calcium may be due to an inhibition of energy requiring steps in the final phase of the secretory process.(ABSTRACT TRUNCATED AT 250 WORDS)

ラット腹腔肥満細胞からのアナフィラキシー性histamine遊離に対するdisodium cromoglycate, 6, 7-dihydro-6, 8, 8, 10-tetramethyl-8H-pyrano[3, 2-G]chromon-2-carboxylic acid (EAA)およびtranilastの抑制効果-細胞外Ca<sup>2+</sup>の影響および交叉タキフィラキシーの成立-

ラット腹腔肥満細胞からのアナフィラキシー性histamine遊離に対するdisodium cromoglycate, 6, 7-dihydro-6, 8, 8, 10-tetramethyl-8H-pyrano[3, 2-G]chromon-2-carboxylic acid (EAA)およびtranilastの抑制効果-細胞外Ca<sup>2+</sup>の影響および交叉タキフィラキシーの成立-

Inhibition of anaphylactic histamine release and pulmonary distress in rats by nonspecific IgE.

Myeloma IgE, obtained from ascitic fluid of rats previously inoculated with the IgE-producing cell line IR-162, was administered in prophylactic and therapeutic regimens to rats passively and actively sensitized to ovalbumin. Administration of myeloma IgE prior to passive sensitization resulted in approximately 95% inhibition of anaphylactic histamine release and significant protection from anaphylactic pulmonary distress. Myeloma IgE treatment prior and subsequent to active sensitization brought about a 70-80% inhibition of anaphylactic histamine release. A similar pattern of protection was seen in animals that received 5 but not 3 weekly myeloma IgE treatments subsequent to active sensitization. These findings indicate that treatment with nonspecific IgE prior to sensitization is effective in blocking anaphylactic reactions but competition with cell-bound IgE in sensitized animals requires prolonged administration of relatively large quantities of 'nonsense' IgE.

Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.

Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.

Histamine-containing cells from bronchial lavage of macaque monkeys. Time course and inhibition of anaphylactic histamine release.

Bronchial lavage of rhesus and cynomolgus monkeys provided leucocyte suspensions with viable histamine-containing cells (HCC) as 1--8% of the white cell population. These HCC released histamine or challenge with antiserum to human IgE. HCC from 2 monkeys with pulmonary and cutaneous hypersensitivity to Ascaris antigen (AA) released histamine on challenge with AA. The extent of histamine release was related to the concentration of antigen and antiserum, and histamine release was complete within 10 min of challenge. (+/-)Salbutamol and (-)isoprenaline were potent inhibitors of anaphylactic histamine release from HCC, but disodium cromoglycate and AH 9679 were relatively poor inhibitors. The HCC system combines the reproducibility of a cell suspension with a response to drugs similar to that of human lung fragments.

Inhibition of anaphylactic histamine release by complexes of lidocaine with zinc

Inhibition of anaphylactic histamine release by complexes of lidocaine with zinc

Diisopropylfluorophosphate-evoked inhibition of anaphylactic histamine release from human skin: decrease of the inhibition by storing the skin specimens

Antigen-induced histamine release from human skin slices passively sensitized with reaginic serum in vitro was inhibited by DFP, suggesting involvement of serine esterase activation in the reaction. The magnitude of DFP-evoked inhibition of the histamine release was not the same in each skin sample and no correlationship was observed between the magnitude of the DFP-evoked inhibition of the histamine release and that of the histamine release in the absence of DFP. The magnitude of the histamine release in the presence of DFP was smaller in the fresh skin than in the stored skin, whereas that in the absence of DFP was greater in the former than in the latter. The inhibitory effect of cytochalasin B on the anaphylactic histamine release from fresh and stored human skin was the reverse of the effect of DFP. The present results indicate that the magnitude of anaphylactic histamine release from human skin does not match that of the activation of serine esterase in the reaction, suggesting the possibility that there may be some factor modulating the activation of serine esterase in the anaphylactic reaction in human skin.

Further studies on the tachyphylaxis to DSCG. The effects of concentration and temperature.

The tachyphylaxis to DSCG's inhibition of anaphylactic histamine release has been demonstrated in passively sensitized rat lung fragments. The induction of tachyphylaxis appears to depend on the concentration of the drug and the length of pretreatment. Tachyphylaxis is relatively independent of the concentration of the second exposure to DSCG. The development of tachyphylaxis is highly temperature dependent; it can be prevented by cooling the tissues to 2-4 degrees C after a brief (30 sec) preincubation with DSCG. It is suggested that DSCG inhibits histamine release by binding to 'receptor' site(s). Once the site is occupied by DSCG, it is modified by a temperature-dependent process, thus losing the ability as a 'receptor' for inhibition of histamine release. The tachyphylaxis is the result of such a modification.

Inhibition of anaphylactic histamine release by Forssman antiserum. II. Mechanism of inhibition.

The mechanism was studied of the inhibitory effect of IgG Forssman antibody on anaphylactic sensitization in the guinea pig lung. Two possibilities were considered to explain the inhibitory effect: either the Forssman antibody-antigen interaction occurred on the mast cell, allowing the F(ab′)<sub>2</sub> portion to interfere with the Fc receptor(s) for anaphylactic antibody; or the interaction took place adjacent to the mast cell allowing the Fc portion to occupy the receptors for anaphylactic antibody. These studies were made possible in part by developing a method for preparing mast cell suspensions from guinea pig lung. The mast cells were viable but released histamine only on treatment with compound 48/80 and not with anaphylatoxin, soluble immune complexes or with active or passive anaphylactic sensitization. Mast cells incubated with Forssman antibody and complement showed no evidence of injury as judged by electron microscopy, suggesting that they did not contain Forssman antigen. The absence of Forssman antigen from mast cells was substantiated further by studies of mixed agglutination and fluorescence microscopy. Also, pepsin digestion of Forssman antibody resulted in a loss of the ability to inhibit the histamine-releasing activity of soluble immune complexes, indicating that the F(ab′)<sub>2</sub> portion alone was not sufficient to sustain the inhibitory process. It was concluded that the inhibitory effect of IgG Forssman antibody was due to union with interstitial Forssman antigen adjacent to mast cells, allowing the Fc portion of the Forssman antibody to irreversibly occupy the mast cell Fc receptor(s) for anaphylactic antibody.

Drug inhibition of anaphylactic histamine release from peritoneal cells of rats infected with Toxocara canis.

An experimental model for studying anaphylactic histamine release from rat peritoneal cells in vitro is described. Rats were sensitized by feeding the infective eggs of ttoxocara canis, the antigen being prepared from the infective eggs. The characteristics of histamine release are comparable with those found for other anaphylactic systems. Addition of 0.2% inactivated normal rat serum to the incubation media reduced the spontaneous histamine release from 11.5 +/- 1.9% to 3.1 +/- 1.6% (mean +/- SD) of total histamine, whereas the corresponding figure for anaphylactic histamine release was 41.3 +/- 19.7%. Both disodium cromoglycate (DSCG) and levamisole produced a dose-related inhibition of histamine release, with DSCG being the more potent drug.

Effect of cromoglycate on anaphylactic histamine release from rat peritoneal mast cells.

Cromoglycate (1-30 muM) produced a concentration-dependent inhibition of anaphylactic histamine release from actively sensitized rat peritoneal mast cells but at lower concentrations (0.01-0.1 muM) occasionally produced a concentration-dependent enhancement of histamine release.

The action of lanthanum and manganese on anaphylactic histamine secretion.

1. In the concentration range 1 nM to 1 muM, lanthanum inhibited the calcium-dependent component of anaphylactic histamine release, but was without effect on the component which was independent of calcium.2. The inhibition of anaphylactic histamine release by lanthanum can be reversed by increasing the calcium ion concentration. The pA(2) for the lanthanum-receptor interaction was found to be 7.6.3. Lanthanum also inhibited the activation of anaphylactic histamine release by strontium ions.4. The inhibition of anaphylactic histamine release by lanthanum was reversed by eluting the lanthanum from the cells.5. In the concentration range 1 to 300 nM, lanthanum had no effect on the histamine release induced by compound 48/80 in a calcium-free medium, but the effect of calcium on the istamine release by compound 48/80 was antagonized by lanthanum in this range of concentrations.6. At concentrations of 10 muM and greater, lanthanum induced a release of histamine in the absence of antigen.7. In the concentration range 0.5 to 4.0 mM, manganese inhibited the calcium-dependent component of anaphylactic histamine release, but was without effect on the component which is independent of calcium. The inhibition of anaphylactic histamine release by manganese could be reversed by increasing the calcium ion concentration.

Inhibition of anaphylactic histamine release by glucose-6-phosphate product of glycogenolysis mediated by cyclic AMP

Inhibition of anaphylactic histamine release by glucose-6-phosphate product of glycogenolysis mediated by cyclic AMP

Inhibition of Anaphylactic Histamine Release by 2-Deoxyglucose

THE inhibition of anaphylactic histamine release by lack of oxygen1–3 suggested the possibility that the metabolism of glucose by the oxidative pathway might be involved in the process. However, glucose itself caused no stimulation of histamine release in my experiments4, although such stimulation has been reported by others5,6. It is possible that the stimulant effect of glucose is observed only when the tissue is depleted of endogenous substrate during its preparation. It should then be possible to inhibit histamine release even in the presence of endogenous substrate with 2-deoxyglucose, which blocks glucose utilization beyond glucose-6-phosphate stage7. Moreover, it has been shown that the inhibition of histamine release by anoxia can be partially reversed by glucose6,8. If this reversal depends on the glycolytic breakdown of glucose, 2-deoxyglucose would be expected to block it. In the present investigation, therefore, the effect of 2-deoxyglucose on anaphylactic histamine release was studied both under aerobic and anaerobic conditions.

MECHANISM OF HISTAMINE-RELEASE INHIBITION BY NICOTINAMIDE IN IN VITRO ANTIGEN-ANTIBODY REACTION

1. Nicotinamide inhibits histamine release by antigen from chopped lung tissue of a sensitized guinea pig. Addition of succinate potentiates this histamine release and accompanying increase in oxygen uptake. However, nicotinamide, though it inhibits increased release of histamine, does not inhibit the increased uptake of oxygen.2. Histamine release from guinea pig lung by sinomenine, compound 48/80, and decylamine, whose action is not considered to involve enzymatic process, differing from that of antigen, is also inhibited by nicotinamide.3. Nicotinamide inhibits anaphylactic contraction of guinea pig ileum and, apparently weakens passive cutaneous anaphylaxis.4. Inhibition of anaphylactic histamine release and contraction of plain muscle by nicotinamide does not prevent desensitization. The plain muscle, from which nicotinamide had been washed off, is capable of undergoing contraction in response to the antigen. Consequently, nicotinamide does not inhibit the union of antigen and antibody.5. Nicotinamide analogs which are DPNase inhibitor, such as nicotinic acid, isonicotinic acid hydrazide, pyridine-3-sulfonic acid, and iproniazid, also inhibit histamine release by antigen in various degrees.6. There is no difference in DPNase activity between sensitized and unsensitized guinea pig lungs. Antigen does not cause any observable change in the DPNase activity of sensitized guinea pig lung. Partially purified bovine spleen DPNase does not increase the release of histamine in vitro, either from the chopped lung tissue of a guinea pig or from subcellular large granules of a dog liver.7. The result, of present series of experiments suggests that the inhibition of histamine release by nicotinamide in antigen-antibody reaction is not the result of inhibition of DPNase but rather is of a type that blocks linking of chemical stimulation, caused by antigen-antibody union, with allergic changes proceeding inside the cell, by a mechanism different from that of respiratory enzyme inhibitors.