Radiation-released histamine in the rhesus monkey as modified by mast-cell depletion and antihistamine.

4000 rads of mixed gamma neutron radiation administered to rhesus monkeys released a significant amount of histamine into their circulation. When the monkeys were treated with a mast-cell histamine depleter (compound 48/80) for 4 days and then irradiated, no increase in circulating histamine was seen. When 48/80 was give 20 min after irradiation, only a slight increase in histamine was seen, indicating that 4000 rads had released most of the mast-cell histamine.     

Die Aktivität der alkalischen Phosphatase im Rattenharn nach Mastzelldegranulierung

Summary Alkaline phosphatase activity was determined in rat urine under normal conditions (80 animals) and following mast cell depletion (30 animals). A statistically significant increase in urinary APA was found after administration of the mast-cell depleting compound 48/80. This fourfold increase over normal activity is due to renal changes caused by shock.     

Histaminantagonistische Wirkungen von Adrenochrom-Monosemicarbazon

Summary In experiments on the skin of the guinea pig, the monosemicarbazone of adrenochrome is shown to prevent increase of vascular permeability due to intradermal injection of histamine or endogenous histamine liberating substance 48/80. By simultaneous intradermal injection with histamine or 48/80, it is equally effective as specific antihistamines in suppressing the skin reaction to 48/80, whereas the antihistamines are considerably stronger antagonists to exogenous histamine. Administered intraperitoneally, adrenochrome monosemicarbazone shows about the same order of antagonistic efficacy as the typical antihistamines. The findings are briefly discussed.

---

---

« Adrenoxyl » ORION Helsinki, unter Lizenz LABAZ Brüssel.     

Stimulation of histamine synthesis in rat mast cells by compound 48/80 in vitro

The histamine content of rat peritoneal fluid cells is doubled within 20 min by 0.5 microgram/ml of compound 48/80. Histamine catabolism inhibitors do not reproduce this effect; cells pre-incubated with alpha-fluoromethylhistidine are unresponsive to compound 48/80 which therefore activates pre-formed histidine decarboxylase rather than 'inducing' it. Non-mast cells showed no change after treatment with compound 48/80.     

Histamine production in mixed culture between allograft donor and recipient lymphocytes]

An increased production of histamine has been demonstrated during mixed cultures between allograft donor and recipient lymphocytes. This phenomenon could result from the action of a non-dialysable factor released by recipient cells in the presence of donor cells. This factor is able to increase histamine production from normal spleen cells. Little or no increase in histamine production is found during primary and mixed lymphocyte cultures (without previous allograft).     

Die Leucinaminopeptidaseaktivität des Rattenharnes nach Verabreichung einer mastzellerschöpfenden Substanz

Summary LAP activity was determined in rat urine under normal conditions and following mast cell depletion by compound 48/80. A statistically significant increase in urinary LAP activity is found after administration of compound 48/80. This increase is due to mast cell depletion and the resulting anaphylactoid reaction.     

Stimulation of histamine synthesis in rat mast cells by compound 48/80 in vitro

Summary The histamine content of rat peritoneal fluid cells is doubled within 20 min by 0.5 g/ml of compound 48/80. Histamine catabolism inhibitors do not reproduce this effect; cells pre-incubated with -fluoromethylhistidine are unresponsive to compound 48/80 which therefore activates pre-formed histidine decarboxylase rather than inducing it. Non-mast cells showed no change after treatment with compound 48/80.     

«Bindung» eines synthetischen Polypeptides (Hypertensin) an Heparin und Freisetzung des Peptides durch Compound 48/80in vitro

Summary It is shown that a synthetic octapeptide, hypertensin, can be bound to heparinin vitro in a fashion similar to that of histamine. Hypertensin can be liberated from this complex by Compound 48/80.     

Compartmentalized growth of hemopoietic stem cells within mouse Friend leukemic spleens

Summary A dose of 4000 rads (r) to the central portion of mouse spleens followed by Friend erythroleukemic virus infection created independent compartments where hemopoietic stem cells exhibited distinct growth kinetics. Rather than suggesting autonomous proliferation, the stem cell kinetics were indicative of the control excercised by the local microenvironment upon stem cell growth within each compartment.Acknowledgments. This work was supported in part by a grant (014077) from the American Medical Association Eduation and research Foundation, Chicago, Illinois. We also wish to thank Priscilla Brown and Peter Brown for their expertise and patience in preparing the photograph for this report.     

Nitroglycerin inhibits the phosphorylation of intermediate filament proteins rather than myosin light chain on porcine coronary artery sustained contraction

The smooth muscle relaxation induced by nitroglycerin is hypothesized to be mediated by an increase in the cytoplasmic concentration of guanosine 3′,5′-monophosphate (cGMP) and subsequent dephosphorylation of the 20-kilodalton myosin light chain (MLC). We investigated this hypothesis in procine coronary arterial smooth muscle stimulated with histamine (3 μM) or K⁺ (30 mM). Stimulation of [³²P]Pi-labeled muscle with histamine or K⁺ for 2 min resulted in a four- or 6.2-fold increase, respectively, in the incorporation of³²P into MLC. After 48 min of exposure to histamine. MLC phosphorylation decreased to the basal level and the phosphorylation of desmin, synemin, and of three unidentified cytosolic proteins was increased. K⁺ stimulation resulted in a sustained increase of MLC phosphorylation but had no effect on the phosphorylation of desmin, synemin, or the three unidentified cytosolic proteins. Application of nitroglycerin (1 μM) 48 min after histamine stimulation inhibited the phosphorylation of desmin, synemin, and the three cytosolic proteins. The sustained phase of histamine-induced contraction was also inhibited to a greater extent then the acute phase of histamine-induced contraction and both the acute and sustained phases of K⁺-induced contraction. These results suggest that MLC phosphorylation is required for both phases of K⁺-induced contraction, whereas phosphorylation of intermediate filament proteins is required for the sustained phase of histamine-induced contraction. Intermediate filament proteins, rather than MLC, may also be the target for the relaxant action of nitroglycerin during histamine-induced sustained contraction.     

Frühe Stadien der Erholung bei bestrahlten ratten und Mäusen

Summary A split dose experiment was performed in 12-, 24- or 32-day-old Wistar rats. About 4000 animals were used. The first dose given was 200 R whole-body X-irradiation in the 2 younger groups, and 260 R in the oldest group. At intervals from 6–48 h after the first, a second irradiation was given in order to estimate the LD50(30). No recovery was seen in terms of the LD50(30) differences between preirradiated and normal animals 6 h after the first dose. At the 12 h interval marked recovery was found in all 3 age groups, but less recovery was apparent at the later intervals.     

Influence de l'anaérobiose et de différentes tensions d'oxygène sur la libération d'histamine dans la réaction anaphylactiquein vitro

Summary The influence of anaerobiose and of varied oxygen tensions upon respiration and histamine release during anaphylactic reaction in guineapig lung slicesin vitro was studied.No histamine was liberated in the absence of oxygen. With increasing oxygen tensions, increasing histamine quantities were released; these quantities reached the control values when the atmosphere contained 10% oxygen.These results indicate that the mechanism of histamine release in the anaphylactic reaction is linked with the aerobic metabolism of the cell.

---

---

Boursicrs du Consclho Nacional de Pesquisas.     

Azelastine inhibits bronchial hyperreactivity to acetylcholine in guinea pigs

Contractile responses to acetylcholine were measured using isolated tracheae obtained from actively sensitized guinea pigs 0.5, 1, 5, 20, 24, 48 and 72 h after antigen challenge. Tracheal contractions to acetylcholine and to histamine were significantly increased 20 h but not 0.5, 1, 5, 24, 48 and 72 h after antigen challenge indicating bronchial hyperreactivity. When animals were pretreated with azelastine and then exposed to antigen challenge, concentration-response curve to acetylcholine did not differ from that obtained in control (non-challenged) tracheae. It is likely that azelastine is able to inhibit bronchial hyperresponsiveness to chemical mediators of bronchial asthma.     

Measurement of polyethylene glycol 4000: Effect of storage and freeze thawing in biological fluids

Summary The effects of storage and freeze-thawing on polyethylene glycol 4000 (PEG 4000) and¹⁴C PEG 4000 in a solution of NaCl (150 mmoles/l) containing varying amounts of human albumin were studied. Results showed that the analysis of both PEG 4000 and¹⁴C PEG 4000 is likely to be inaccurate in these fluids if the specimens have been freeze-stored, thawed and refrozen several times during a period of several weeks. This seems to be due to the freeze-thawing process itself rather than the actual storage. The amount of protein in the samples may increase the fall in estimated levels of polyethylene glycol observed.     

Dopamine-beta-hydroxylase activity in adrenal gland and spleen of rats after fasting and cold exposure

Summary Fasting (48 h) results in dopamine-beta-hydroxylase (DBH) release both in adrenal gland and spleen, suggestive of an increase in the activity of these organs. Cold exposure (48 h) produces a dissociation of the, sympathoadrenal response. When both stimuli are simultaneously employed, the DBH response suggests the preponderance of the response to fasting. Plasma DBH is decreased in all groups studied, this could be due to its half-life and the splenic DBH depletion.This work was supported by a grant of Fondo de Investigaciones Sanitarias de la Seguridad Social, No. 83/0905.     

Biological implications of preformed mast cell mediators

Mast cells store an impressive array of preformed compounds (mediators) in their secretory granules. When mast cells degranulate, these are released and have a profound impact on any condition in which mast cell degranulation occurs. The preformed mast cell mediators include well-known substances such as histamine, proteoglycans, proteases, and preformed cytokines, as well as several recently identified compounds. Mast cells have recently been implicated in a large number of novel pathological settings in addition to their well-established contribution to allergic reactions, and there is consequently a large current interest in the molecular mechanisms by which mast cells act in the context of a given condition. In many cases, preformed mast cell mediators have been shown to account for functions ascribed to mast cells, and these compounds are hence emerging as major players in numerous pathologies. In this review we summarize the current knowledge of preformed mast cell mediators.     

Activation-induced cellular accumulation of histamine in immature but not mature murine mast cells

Mast cell activation involves the rapid release of inflammatory mediators, including histamine, from intracellular granules. The cells are capable of regranulation and multiple rounds of activation. The goal of this study was to determine if there are changes in the content of pre-formed mast cell mediators after a round of activation. After 24 h, the histamine content of bone marrow-derived mast cells (BMMC), but not that of peritoneal mast cells, exceeded the amount in resting cells. Accumulation of histamine in BMMC peaked at 72 h of activation, and returned toward preactivation levels by 96 h. The increase in histamine content was accompanied by an increase in the gene expression of histidine decarboxylase. No increases in beta hexosaminidase or murine mast cell protease-6 were observed. These findings indicate that BMMC respond to activation by increasing total cell-associated histamine content. This increase may be important to the response of these cells upon subsequent exposure to antigens.     

Histamine binding to H2 receptors stimulates phospholipid methylation in mast cells

Summary Rat peritoneal mast cells incubated in vitro in the presence of L-[methyl-³H] methionine and exposed to histamine undergo a rapid but transient increase in phospholipid methylation. By using specific H₁- and H₂-receptor antagonists, and histamine analogues differing in their H₂-receptor agonist potency, it has been demonstrated that this metabolic event is dependent on histamine binding to H₂-receptors.We are grateful to Smith Kline and French Laboratories for the generous gift of histamine analogues.     

Effect of the mast cell disruptor B.W. 48/80 on dietary atherosclerosis in the male rabbit

Zusammenfassung Mit Cholesterin ernährte Kaninchen, denen gleichzeitig Compound 48/80 injiziert wurde, wiesen gegenüber nur mit Cholesterinzusatz gefütterten Tieren geringere Atheromatose des Aortenbogens auf. Compound 48/80 rief auch eine Verminderung des Serumcholesteringehaltes hervor. Unter dem Einfluss von Compound 48/80 schien ein beschleunigter Abbau der atheromatösen Plaques einzusetzen bevor noch eine Verminderung des Serumcholesterins auftrat. Es wird vermutet, dass der Schutz von Compound 48/80 gegen die durch Diät erzeugte Atheromatose des Kaninchens auf einer Veränderung des arteriellen Glykosaminglykans beruht.     

Insulin secretion and (pro)insulin biosynthesis of cultured mice islets after glibenclamide loading in vitro

Isolated islets from C57Bl/6J mice exposed to 10 mmoles/l glucose supplemented with 5 micrograms/ml glibenclamide for 48 h released significantly less insulin in the subsequent short-time incubation than untreated controls (without glibenclamide), whereas insulin biosynthesis was not suppressed by glibenclamide treatment.