Cz. Maśliński

The Inhibitory Effect of Nicotinamide on Asthma-Like Symptoms and Eosinophilia in Guinea Pigs, Anaphylactic Mast Cell Degranulation in Mice, and Histamine Release from Rat Isolated Peritoneal Mast Cells by Compound 48/80

The prior treatment of guinea pigs with nicotinamide diminished the symptoms of experimental bronchial asthma and the intensity of anaphylactic shock. Nicotinamide was also found to inhibit anaphylactic mast cell degranulation in mice and histamine release from rat-isolated peritoneal mast cells by compound 48/80. The role of nicotinamide in bronchial asthma is discussed.

Histamine content and synthesis in central and pheripheral nerve structures during stress

Histamine content and histidine decarboxylase activity in cortex and hypothalamus, together with histamine content in peripheral nervous structures were examined in normal and electrically stressed guinea-pigs. A significant increase in histidine decarboxylase activity in hypothalamus and cortex together with concomitant decrease in histamine content in hypothalamus have been found. Electric shock causes also a decrease in histamine content in spinal cord, spinal ganglia, dorsal roots and sensory nerve. The function of histamine in nervous system is discussed.

Failure of acetylcholine to release histamine from rat mast cells

The action of various salts of acetylcholine on isolated mast cells from Wistar and F1 hybrids of Wistar and August rats was investigated.None of the acetylcholine salts within the concentration range 10−12M to 10−2M was able to release histamine either from Wistar or from hybrid mast cells. Compound 48/80, used as a control, was active in both cases.The results obtained are in opposition to some recent reports. The possible reasons for these contradictions are discussed.

The effects of histamine liberators and exogenous histamine on wound healing in rat.

The effects of compound 48/80, adenosine-5-triphosphate (ATP) and exogenous histamine (Hi) on the healing of excised surface wound and tensile strength of surgical skin wound in rat were studied.The chemicals were injected directly into the wounded area. 48/80, ATP and exogenous Hi were found to stimulate the wound healing as measured by collagen formation, tensile strength examination and a measurement of the surface circular wound. When given separately, the order of activities was: 48/80>ATP>Hi; when administered together as a mixture, compound 48/80, ATP and exogenous Hi also accelerated the wound healing. The mixture shortened the healing process by about 5 days as compared with 17 days in control.

Histamine and its catabolism in tumour-bearing rat and mouse.

The hypothesls that fallure of histamine (Hi)-mediated inter and intracellulary cell-cell communication may be involved in the control of cellular growth has been tested in leukaemia-bearing mice and fibrosarcoma-bearing rats.In all examined tissues of mice bearing leukaemia L1210 cells and rats bearing methylcholanthrene fibrosarcoma histamine content was higher than in controls.Tissues of fibrosarcoma-bearing rats more intensively metabolized14C-Hi and oxidative pathway was predominat. Histamine metabolic activity as well as histamine catabolic pathways do not differ in leukaemic mice as compared with the controls.

Inhibition by nicotinamide of a homologous PCA reaction and antigen-induced histamine release from isolated rat peritoneal mast cells

(1) The inhibition of Histamine release by nicotinamide has been known about for a long time but its mode of action as well as the mechanism involved has remained ill-understood despite numerous hypothesis [1, 2, 5]. (a) In mast cells isolated from the rat peritoneum we have shown that nicotinamide (40 mM) will reduce by 2/s rds the release of histamine produced by 0.4 ~g/ml of compound 48/80. The liberation by the peptone of Witte is also reduced. However, compared to the inhibition of release by cyanide of mercury its action is weak. (b) In the dog, in vivo, taken as its own control, a dose of 150 m s / k s nicotinamide will reduce, in certain cases, the release of histamine produced by the injection of 100 ms /ks of the peptone of Witte. (2) Under other experimental conditions, on the other hand, nicotinamide is capable of liberating histamine, particularly when high concentrations are used [3]. Indeed, when one measures the insutttation resistance and arterial pressure in the anaesthetized guinea-pig, intravenous injection of 200 to 400 ms /ks nicotinamide immediately produces a violent and transient increase in insufflation resistance associated with a parallel hypotension. Previous injection of 5 ms /ks mepyramine prevents these effects. Using the isolated, perfused guinea-pig lung we have obtained a release of histamine of 0.1 ~xg/g rain when perfusing 50 m M nicotinamide at a rate of 5 ml/min. Also it has been found that the addition of nicotinamide to a preparation of chopped guinea-pig lung will show a release of histamine proportional to the dose added. Released histamine was measured by automated fluorometric analysis, the quantity of histamine dihydrochloride released being of the order of 1 ~g/g lung tissue in the presence of 125 m M nicotinamide per ml in contact with lung tissue. Values of 2 ~g for 250 m M and 3 ~xg for 374 m M were also obtained. Nicotinamide appears to inhibit nicotinamide-adenine-dinucleotidase and thus reduce histamine liberation. This mechanism must be clarified as well as the role of nicotinamide in the release of histamine.

The role of histamine in wound healing. II. The effect of antagonists and agonists of histamine receptors (H1 and H2) on collagen levels in granulation tissue

The effects of mepyramine (H1-receptor antagonist), cimetidine (H2-receptor antagonist), IEM-813 (H1-receptor agonist) and 4-Met-Hi (H2-receptor agonist) on collagenogenesis processes in subcutaneous implanted sponges of rats were studied. Administration into sponges of cimetidine 30 min before histamine injection blocked both the stimulatory effect of low histamine doses and the inhibitory effect of high histamine doses on collagen formation. Low doses of 4-Met-Hi increased collagen levels but reduced the levels at high doses. Mepyramine and IEM-813 did not influence collagen biosynthesis.

Cholinergic link in the histamine-mediated increase in homovanillic acid in the rat striatum

Adminstration of 500 μg of histamine into the lateral brain ventricle of the rat produced a 50% increase in striatal HVA. The DA level remained unchanged. The histaminemediated elevation of HVA was abolished by pre-treatment with the antihistaminic drug — mepyramine. Moreover atropine significantly reduced the histamine-induced increase of HVA.It is concluded that histamine primarily activates cholinergic neurons and that the changes in DA metabolism are a consequence of an increased cholinergic activity.

Antihistaminic action of nicotinamide

It has been shown previously that the respiration of rat mast cells is temporarily stimulated for 15-20 minutes after histamine release is initiated by anaphylactlc reaction in vitro [2]. In these experiments measurements of oxygen uptake could not be resumed until 4-5 minutes after mixing the mast cells with antigen but, by extrapolation, the stimulation appeared to have been initiated at the time of the contact of the mast cells with the antigen. Glucose is apparently an important substrate for the rat mast cells. This is indicated by the stimulation of mast cell respiration by glucose [3] and the high rate of anaerobic and aerobic glycolysis in these cells [1]. In the present series of experiments mast cell populations from rat peritoneal cavity, isolated by differential centrifugation in con-

Catalepsia-like symptoms produced by histidine in rats

partial and 44,58 and 67 7oo inhibition are found for imidazole, 2-methylimidazole and 2-ethylimidazole. N-Methylimidazole also exerts a slight inhibitory action upon the effects of imidazole. Three new compounds, which were supposed to be imidazole receptor inhibitors, have been synthesized. The effect of these compounds N-(sec-butyl)imidazole, N-(n-butyl)imidazole and N-allytimidazole, upon guinea-pig auricles is quite unexpected. Though they do not block the imidazole receptor, they strongly effect the heart by an increase of the amplitude and of the frequency of contraction. The ECG examination shows that imidazole in a dose of 0.2 g/kg i.v. produces a transitory sinus bradycardia, in a dose of 0.4 g/kg i.v. a sinus arrhythmia with a bradycardia. 2-Methylimidazole in a dose of 0.2 g/kg i.v. produces a transitory sinus bradycardia and in a dose of 0.4 g/kg i.v. a ventricular arrhythmia and hemi block. N-(n-Butyl)imidazole is found to be very toxic, since it produces a pronounced bradycardia and branch blocks. The decrease in the concentration of Ca ions from 1.8 m M to 0.9 m M does not change the efficacy of imidazole on the guinea-pig auricles. These results differ from our previous findings obtained on the isolated nervous-muscular preparation of the frog. In this preparation the decrease in the concentration of Ca ions to 0.9 m M reduces the inotropic action of imidazole by about 30% and shortens the time of its action.