Wheal and flare reactions as well as a late cutaneous allergic reaction (LCAR) were induced by anti-human IgE in healthy subjects. The effect of the beta 2-adrenoceptor stimulant terbutaline, the histamine-1 (H1) receptor blocking agent mepyramine and the synthetic glucocorticoid betamethasone on these reactions was studied. All administrations were given intradermally (i.d.). The immediate reaction to anti-IgE was inhibited by 3 micrograms terbutaline and 30 micrograms mepyramine (P less than 0.01) whereas 50 micrograms betamethasone had no effects. Terbutaline had no effect on the flare response induced by i.d. injected histamine but a slight effect on whealing. Terbutaline and mepyramine weakly reduced the LCAR throughout the observation period of 24 h (P less than 0.01). In contrast, betamethasone almost completely abolished the LCAR. It is concluded that the two phases of the skin reaction to anti-IgE are interrelated since an inhibition of the early phase was followed by an attenuation of the LCAR. The mechanism of action of steroids seems to differ fundamentally from that of other anti-allergic drugs since inhibition of the early step in the reaction is not essential to the action on the late step. It is further suggested that terbutaline inhibits anti-IgE-mediated cutaneous reactions by inhibition of the mast cell release reaction.
STRANDBERG, K. and B. UVNAS. Purification and flroperties of the slow reacting substance formed in the cat paw perfused with compound 48/80. Acta physiol. scand. 1971. 82. 358-374.Cat paws were perfused with a physiological salt solution containing compound 48/80. In addition to histamine, a principle producing a slow sustained contraction of the isolated guineapig ileum appeared in the effluent. This slow reacting substance (SRS) was purified by ethanol extraction, solvent partition, silicic acid and anion exchange chromatography. The overall recovery was 10-20 per cent, calculated from the non-histamine smooth muscle stimulating activity of the ethanolic extract. The purification calculated from the crude lipid extract was about 200-fold. The purified material was diaJysable, thermostable at neutral pH and more labile in acid than in alkaline milieu. I t behaved homogenously on thin layer chromatography in several systems. The most marked biological effects were contraction of the isolated guineapig ileum and the human bronchus, increases in the bronchial resistance in guinea-pigs in vivo, in the colouration (Evan's blue dye i.v.) of guinea-pig skin after intradermal injection and in the blood flow in the cat hindlimb after intraarterial injection. Treatment of the purified material with N,N'-carbo-di-p-tolylimide, phenyl isocyanate, iodine monobromide, potassium permanganate or acetic anhydride abolished or greatly reduced the biological activity. Incubation of SRS with 15-hydroxy prostaglandin dehydrogenase in the presence of NAD' resulted in no loss of biological activity. Together the results indicate that SRS is a biologically active carboxylic acid with hydroxyl groups and one or more double bonds but probably of nonprostaglandin nature.
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