Czesław Maśliński

The action of local anaesthetics on histamine release

Abstract The effect of the local anaesthetics lidocaine, procaine and tetracaine on compound 48/80-induced histamine release from isolated rat mast cells has been investigated. They inhibited histamine release in a dose-dependent manner; at a concentration of 20 mM there was almost total inhibition of histamine release by lidocaine and about 75% inhibition by procaine. Tetracaine exerted a biphasic effect: at concentrations below 1 mM it inhibited, but at concentrations above 1 mM it potentiated histamine release. The inhibitory effect of lidocaine on compound 48/80-evoked histamine release was dependent upon the time of preincubation of mast cells with this anaesthetic and it persisted after washing the cells and resuspension in a lidocaine-free medium. An increase of calcium ions antagonized the inhibitory action of lidocaine. These results can be explained by (1) blockade of membrane receptors for calcium binding which leads to a decrease in intracellular calcium concentration and (2) increase of cellular cyclic AMP content which subsequently inhibits the releasing process.

Interference of aldehyde metabolizing enzymes with diamine oxidase/histaminase/activity as determined by 14C putrescine method.

Abstract The Δ 1 pyrroline formation, as an indicator of diamine oxidase activity according to Okuyama and Kobayashi 14 C putrescine test [1], has been investigated in several tissue homogenates. When guinea pig liver homogenate was used as a source of enzyme in the presence of aldehyde dehydrogenase inhibitors chloral hydrate and acetaldehyde the level of formation Δ 1 pyrroline was strongly increased in a dose-dependent manner. Also inhibition of aldehyde reductase by phenobarbital enhanced Δ 1 pyrroline formation, but to a lesser degree. In other tissues, with very high initial diamine oxidase activity (rat intestine, dog kidney) or with very low diamine oxidase activity (guinea pig skin, dog liver) the influence of these inhibitors was only slight. Pyrazole, an inhibitor of alcohol dehydrogenase exerted only a small effect on Δ 1 pyrroline formation. All aldehyde-metabolizing enzymes inhibitors, except pyrazole, were without effect on purified pea seedling and hog kidney diamine oxidases. The use of aldehyde-metabolizing enzymes inhibitors may help to reveal the real values of diamine oxidase activity, when tissues homogenates are used as a source of enzyme.

Histamine release from mast cells by compound 48/80. The membrane action of zinc.

The influence of both zinc chloride and unsaturated zinc: 8-Hydroxyquinoline (Zn: 8-HQ) complex on histamine release induced by compound 48/80 have been investigated. It was found that the inhibitory action of Zn: 8-HQ complex which is known to be unable to penetrate into the cells and acts on mast cell membrane was more pronounced than the action of zinc alone.These results suggest the membrane mechanism of zinc action. The inhibitory action of zinc depends on compound 48/80 concentration when the 2 chemicals act simultaneously but it is not dependent on 48/80 concentration when zinc was added before the liberator. Zinc potentiated the histamine releasing effect of compound 48/80 when it was added after mast cells degranulation. This effect supports the hypothesis of the ionic binding of histamine in mast cells granules.

A protective action of disodium cromoglycate against the contraction of guinea-pig ileum induced by various pharmacological stimulants

The effect of disodium cromoglycate (DSCG) on the contraction of isolated guinea-pig ileum induced by histamine, acetylcholine and serotonin has been investigated. DSCG protected ileum against all agents tested. The action of DSCG at concentrations of 10−3 to 10−2M was both dose- and time-dependent. Furthermore, DSCG inhibited compound 48/80-induced histamine release from isolated mast cells over the same range of concentrations.The anti-histaminic action of DSCG was reversible and after 2 h the ileum responded normally to histamine.DSCG-induced inhibition of the contractile response to histamine could be overcome by increasing concentrations of histamine but not by extracellular calcium.A mechanism of the action of DSCG, either against the contraction of ileal smooth muscle or against histamine release from mast cells, is discussed with a view to the inhibition of the utilization of calcium ions by both cells.

Conditions for the formation of cyclic compounds between pyridoxal phosphate and 5-hydroxytryptamine or 5-hydroxytryptophan

Abstract5-Hydroxytryptamine (5HT) and 5-hydroxytryptophan (5HTP) form cyclic compounds (probably of the tetrahydro-β-carboline type) with pyridoxal phosphate (PLP). In the first step of reaction a Schiffs base is formed; during incubation it is transformed into a cyclic compound with a maximum absorption spectrum at 330 nm. The degree of cyclization depends on pH and substrate concentrations. One mole of 5HT or 5HTP reacts with one mole of coenzyme. The velocity of cyclization increased with an excess of either 5HT (5HTP) or PLP, without any change in the mole to mole ratio. The formation of cyclic compounds was confirmed by the use of isotopes, separation from substrates being achieved by high-voltage electrophoresis.

In vivo formation of histamine phosphopyridoxal cyclic compounds

A possibility of in vivo formation of cyclic compounds between histamine (Hi) given i.p. and endogenous pyridoxal (PL) or pyridoxal 5′-phosphate (PLP) has been studied. Cyclic compounds of Hi with PL or PLP were found in all tissues examined. Although an increase in Hi levels in tissues enhances the formation of cyclic compounds, no simple relationship between the rate of formation and Hi concentration has been observed. The reaction seems to be limited by endogenous PLP. The cyclic products Hi-PL and HI-PLP were discovered in urine. It is suggested that the process of cyclic compound formation may reduce PLP resources, resulting in a modification of PLP-enzyme activities.

Histamine metabolism in experimental silicosis I. Experiments on the isolated rat lung and on guinea pig lung homogenates and sections

Abstract Isolated rats lungs were perfused by a Van Dyke solution with and without silica dust. The silica dust releases histamine from lung tissue and the liberated histamine exerts its pharmacological effects on the bronchial smooth muscle layer. Liberation of histamine by silica dust leads to an activation of histidine decarboxylase while silica dust itself does not activate the free enzyme in vitro.

Activation of hamster mast cells for IgE - mediated histamine release

The conditions for active sensitization of hamster peritoneal and pleural mast cells and IgE-induced histamine release as well as cell desensitization were defined. Immunization of hamsters with ovalbumin (5 μg) in Al/OH/3 gel (5 mg) with several boosters resulted in sensitization of peritoneal and pleural mast cells; in the presence of extracellular Ca++, pH of medium 7.2 and at 37°C these cells released up to 70% of histamine on the challenge with specific antigen. Partial release was observed when the cells were challenged with antigen in the absence of extracellular calcium. The rate of release is high during the first seconds of activation and is complete at 1 min. 30 min preincubation of peritoneal and pleural mast cells in calcium-free conditions (in the presence of 4 mM EDTA) resulted in complete desensitization of cells to subsequent action of antigen in potimal conditions. The present experiments demonstrate, that hamster peritoneal and pleural mast cells can be a useful model system forin vitro studies of the mechanisms of IgE-induced cell activation.

Gamma-aminobutyric acid (GABA) formation from putrescine in guinea-pig liver during ontogenesis☆

1. The changes in hepatic diamine oxidase (DAO) activity of the foetal and maternal origin and their relations to GABA formation during pregnancy in guinea-pigs are described. 2. Foetal DAO activity continuously increased while the maternal enzyme from the 45th day of gestation onwards decreased. 3. Conversion of putrescine to GABA via oxidative deamination has been detected in the earliest studied day i.e. the 34th.

Histamine has no influence on the oxidative properties of ceruloplasmin.

Abstract Histamine dihydrochloride increases ceruloplasmin-catalyzed reactions with p-phenylenediamine and o-dianisidine. This effect is entirely due to the influence of chloride ions; histamine itself does not alter ceruplasmin activity. The effect of chloride and phosphate ions on ceruloplasmin activity is reported, and the significance of these findings relative to previous assays for amine oxidase is discussed. In addition, the histamine H2-receptor antagonists: burimamide and metiamide were found to cause disappearance of colour formed during o-dianisidine oxidation; this effect probably depends on the thiourea residue.