Effect of phospholipase A2 inhibitor ONO-RS-082 on substance P-induced histamine release from rat peritoneal mast cells.

Rat peritoneal mast cells purified on a Percoll gradient were challenged with substance P (SP) and the effect of phospholipase A2 inhibitor ONO-RS-082 on SP-induced histamine release from the cells was investigated. 10(-5) mol/l SP caused a significant histamine release and the amount of histamine release reached maximum at 1 min after the challenge. ONO-RS-082 inhibited the SP-induced histamine release in a concentration-dependent manner at the concentration from 10(-6) to 10(-4) mol/l, suggesting possible involvement of phospholipase A2 in SP-induced histamine release from rat peritoneal mast cells.     

Extracellular phospholipase A2 and histamine release from rat peritoneal mast cells.

Phospholipase A2 (PLA2) from cobra (Naja naja) venom and PLA2 from porcine pancreas accelerated IgE antibody-mediated histamine release from rat peritoneal mast cells. These enhancements were clearly abrogated by heating the enzymes and pretreatment with parabromophenacyl bromide, mepacrine and antiflammin. Indomethacin (cyclooxygenase inhibitor) and AA-861 (lipoxygenase inhibitor) did not affect the enhancement by PLA2. These results indicate that extracellular PLA2 enhances the IgE antibody-mediated histamine release from rat peritoneal mast cells without the participation of arachidonate.     

Effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on substance P-induced histamine release from rat peritoneal mast cells

12-O-tetradecanoylphorbol-13-acetate (TPA, 1 to 30 ng/ml) produced a dose-related inhibition of substance P (SP)-induced histamine release from rat peritoneal mast cells. TPA itself induced some histamine release over this concentration range (maximum release about 20% of total). Maximum inhibition of SP-induced release by TPA required preincubation with TPA for at least 10 min. The inhibitory action of TPA was observed in the absence as well as in the presence of extracellular calcium (0.4 mM). Inhibition of diacylglycerol kinase by R 59022 or of diacylglycerol lipase by RHC 80267 reduced SP-induced histamine release. Oleolylacetylglycerol (OAG, 50 M) inhibited histamine release induced by SP but was less potent than TPA. It is concluded that protein kinase C activation in rat peritoneal mast cells is associated with inhibition of SP-induced histamine release.     

Effect of dantrolene on histamine release from rat peritoneal mast cells

Dantrolene strongly and dose-dependently inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Dantrolene inhibited Ca²⁺-mobilization from intracellular Ca²⁺-store as well as histamine release in mast cells activated by anti-IgE, the effect on both of these phenomena being closely correlated. These results suggested that the effect of dantrolene on histamine release from rat mast cell might be due to the inhibition of Ca²⁺-release from intracellular Ca²⁺-store.     

Mechanism of histamine release from rat peritoneal mast cells

Summary The present communication endeavours to elucidate the mechanism of histamine release from rat peritoneal mast cells induced by selective histamine liberators.Of the different enzymatic processes involved in secretion the following are considered: ecto-ATPase activity in the mast cell, pro-esterase-esterase conversion during histamine secretion, cyclic AMP and microtubule association/dissociation, phospholipase A₂ and the effect of phospholipid metabolites on secretion, N-methyl transferase and the methylation of phospholipids and the phosphorylation and desphosphorylation of proteins.     

A toxic substance from the sea urchinToxopneustes pileolus induces histamine release from rat peritoneal mast cells

A toxic substance (P-II fraction), fractionated from the pedicellariae of the sea urchinToxopneustes pileulus, dose-dependently caused the histamine release from rat peritoneal mast cells. The histamine release induced by P-II fraction increased with time, while compound 48/80 caused a more rapid histamine release. The dose-response curve for P-II fraction was studied with concentration 0.03–2.0 mg/ml. This reaction was dependent on Ca²⁺ and temperature. When glucose (5.5. mM) was omitted during the incubation step, the histamine release induced by P-II fraction was significantly reduced as compared to that of compound 48/80. Pyruvate reversed this reduction. On the other hand, the histamine release induced by P-II fraction was effectively potentiated by the addition of glucose (11.0 mM), but not that by compound 48/80. These results suggest that P-II fraction-induced histamine release differs from that of compound 48/80 disregards to the effects of glucose, because this histamine release appears to be more sensitive to the glycolytic pathway than compound 48/80-induced histamine release.     

Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the ‘state of equilibrium’ at the cell surface caused by the superfusion (Uvnäs et al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration-dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 μm and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 μm. The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumption in vivo the mast cell delivers histamine to restore the juxtacellular equilibrium.     

Naturally occurring aliphatic polyamines-induced histamine release from rat peritoneal mast cells]

Rat peritoneal mast cells obtained by Percoll gradient were incubated with different concentrations of naturally occurring aliphatic polyamines, spermine and spermidine, at 0.1-10 mM and the amount of histamine release into the supernatant solutions was measured. The addition of each polyamine to the suspensions of the mast cells caused a histamine release in a dose-dependent manner. The histamine release from the cells incubated with each polyamine was rapid and the amount of the histamine release into the supernatant solutions reached maximum at one minute with the incubations.     

Effect of picumast on histamine release from rat cardiac and peritoneal mast cells

Compound 48/80-induced histamine release (HR) from the isolated perfused rat heart was markedly and significantly inhibited by picumast (PIC), possibly by acting as a calmodulin antagonist (CMA) or membrane stabilizer. Trifluoperazine (TFP, another CMA in clinical use) had a similar effect. However, an action as CMA being the basis of inhibition of HR could not be confirmed in another allergy model, namely HR from rat peritoneal mast cells (RPMC). PIC, TFP and two other CMA, W7 andN-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide) failed consistently to inhibit 48/80-induced HR from RPMC, and when used on their own at high concentration these compounds caused HR. PIC and TFP also potentiated the heat-induced haemolysis of rat erythrocytes, i.e. lacked membrane stabilizing effect in this model.     

Mechanisms of vancomycin-induced histamine release from rat peritoneal mast cells

The mechanisms of vancomycin (VCM)-induced histamine release were studied with rat peritoneal mast cells. VCM (>1×10^–3 M) released histamine from the isolated mast cells in a dose-dependent and noncytotoxic manner. In the absence of extracellular Ca²⁺, the histamine release was reduced markedly. When the intracellular Ca²⁺ was depleted, it was further decreased. The Fura-2-loaded single mast cells showed a biphasic increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) by VCM: the first transient and the second sustained components. In the absence of extracellular Ca²⁺, the transient component was unchanged, while the sustained component was eliminated completely. The IP₃ content in the mast cells increased within 10 s after the application of VCM. These results suggest that VCM releases histamine from rat peritoneal mast cells via an IP₃ production and increase in [Ca²⁺]_i.     

Prostaglandin and histamine release from stimulated rat peritoneal mast cells

The production of five prostanoids (PGD₂, PGE₂, PGF₂, 6-oxo-PGF₁, and TxB₂) was examined after mast cell activation. Prostaglandin D₂ (PGD₂) was the major prostanoid produced after stimulation of rat peritoneal mast cells with the calcium ionophore A 23187, compound 48/80 or anti-rat IgE. The amount of PGD₂ generated was not dependent on the quantity of histamine released. The time course of PGD₂ production paralleled the release of histamine following activation with A 23187 or anti-rat IgE but with compound 48/80 release of histamine reached a maximum within 15 sec, whereas production of PGD₂ was apparent only after 5 min and was still increasing at 30 min.     

Auranofin inhibits histamine release from rat peritoneal mast cells.

The effect of auranofin on histamine release from immunologic and non-immunologic activated rat peritoneal mast cells cocultured with 3T3 fibroblasts (MC/3T3) was investigated. When MC/3T3 were preincubated with 2 x 10(-5) M auranofin and thereafter challenged with anti-IgE antibodies, a maximal inhibition of histamine release (86.2%) was obtained. Non-immunological histamine release induced by compound 48/80, substance P and bradykinin was inhibited to a lesser degree, i.e. 36.0%, 37.6% and 24.0% respectively. Simultaneous incubation of auranofin and the stimulating agents resulted in a higher inhibition of histamine release: anti-IgE antibodies--92.0%; compound 48/80--73.5%; substance P--46.1%. We conclude that auranofin effectively reduces histamine release from immunologic and non-immunologic activated mast cells. This may be relevant to the control of allergic reactions.     

Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells.

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the 'state of equilibrium' at the cell surface caused by the superfusion (Uvn?s et al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration-dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 microM and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 microM. The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumption in vivo the mast cell delivers histamine to restore the juxtacellular equilibrium.     

Effect of the carboxylic ionophore monensin on histamine release from rat peritoneal mast cells

The effect of the monovalent carboxylic ionophore monensin, which mediates a one-for-one exchange of intracellular H⁺ for extracellular Na⁺, was investigated in purified rat peritoneal mast cells. Monensin inhibited histamine secretion induced by compound 48/80, adriamycin and the calcium ionophore A23187; the inhibitory effect was maximal when the compound was added at least 10 min before the secretagogues. Washing of cells before addition of the secretagogues did not abolish the inhibitory effect of monensin. On the contrary the carboxylic ionophore was completely ineffective in preventing concanavalin A-induced histamine release.When rat peritoneal mast cells were incubated in the presence of monensin for longer period (up to 5 hours), the substance induced a slow, progressive and dose dependent histamine release, which, at least for lower doses was noncytotoxic. The secretory effect of monensin was still present if the ionophore was washed away after 10 min of incubation, and the incubation continued in drug-free medium. Monensin stimulated histamine secretion was strictly dependent on extracellular Na⁺ concentrations, and independent on extracellular Ca⁺⁺.     

The effect of tartrazine on histamine release from rat peritoneal mast cells

The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 10⁻⁵ to 10⁻²M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 10⁻³ and 10⁻⁴M. Augmentation of ionophore induced release was maximal at between 0–5 min preincubation of the cells with tartrazine.     

Effect of cyclosporin analogues on histamine release from rat peritoneal mast cells and rat basophilic leukaemia cells

Inflammation Research -     

Effect of anti-allergic compounds on histamine release from rat peritoneal mast cells treated with concanavalin A

The anti-allergic drugs theophylline, doxantrazole, quercetin, dibutyryl cyclic AMP, and disodium cromoglycate prevented histamine release induced by concanavalin A in both the presence and absence of extracellular calcium. The compounds were generally most effective in the absence of added calcium and least effective in the simultaneous presence of calcium and phosphatidyl serine. The activity of the test drugs in calcium-free media clearly cannot be explained in terms of their postulated ability to block movement of the ion from the external environment into the cell. Alternative modes of action are thus considered.     

Inhibition of substance P-induced histamine release from rat peritoneal mast cells by ultraviolet light B irradiation: decreased intracellular calcium as a partial mechanism

Background Ultraviolet light irradiation has been shown to suppress immunological reactions of irradiated individuals, however, less attention has been paid to the effects on neurogenic inflammation. Objective We have investigated the effect of ultraviolet light B (UVB) irradiation on substance P (SP)-induced histamine release from rat mast cells. Methods Rat peritoneal mast cells were treated with UVB irradiation and challenged by SP. Histamine release from the cells and intracellular calcium concentrations ([Ca²⁺]i) in the cells were measured. Results UVB irradiation at doses used in the present study did not induce histamine release from mast cells. UVB irradiation at doses from 25 to 200mJ/cm² inhibited 10^–5mol/L SP-induced histamine release in a dose-dependent manner. On the other hand, SP-induced increase of [Ca²⁺]_i was inhibited by UVB irradiation only at doses of 100 and 200 mJ/cm². Conclusion These data suggest that UVB irradiation inhibits histamine release from SP-activated rat peritoneal mast cells partially through the suppression of an increase in [Ca²⁺]_i.     

A peritoneal fluid activator for histamine release from isolated peritoneal mast cells of the rat

A factor present in rat peritoneal fluid has been found to be necessary for optimal release of histamine from peritoneal mast cells by dextran and antigen, but not by concanavalin A. Washed peritoneal mast cells suspended in a physiological medium containing bovine serum albumin require ten-fold higher concentrations of phosphatidyl serine for optimal release by concanavalin A. The peritoneal fluid activator is probably a protein of molecular weight about 180,000 Daltons.     

Naturally occurring aliphatic polyamines-induced histamine release from rat peritoneal mast cells

Rat peritoneal mast cells were incubated with different concentrations of naturally occurring aliphatic polyamines, spermine and spermidine, at 0.1-10 mM and the amount of histamine release into the supernatant solutions was measured. The addition of each polyamine to the suspensions of the mast cells caused a histamine release in a dose-dependent manner. The effect of 10 mM spermine and spermidine was as much as that of 0.5 microgram/ml compound 48/80. The histamine release from the cells incubated with each polyamine was rapid and the amount of histamine release into the supernatant solutions reached a maximum at 1 min with the incubations. 0.1 mM spermine, which in itself could not cause a significant histamine release, showed a tendency to enhance anti-IgE-induced histamine release from the mast cells.