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  • Key words:β-adrenoceptor agonist — Mast cells — Tryptase — TNF-α— Protein tyrosine phosphorylation  (1)
  • 1
    ISSN: 1420-908X
    Keywords: Key words:β-adrenoceptor agonist — Mast cells — Tryptase — TNF-α— Protein tyrosine phosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective: This study aimed to evaluate the abil-ity of S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino) ethyl]-1,3-benzothiazol-2(3H)-one acetate), a novel β 2-adrenoceptor selective agonist derived from marine sponge, to inhibit IgE-mediated activation of human cultured mast cells (HCMC) in vitro.¶Materials and Methods: We examined the effect of S1319 (racemate) on tryptase release and tumor necrosis factor- α (TNF-α) production in HCMC generated from human cord blood cells, after cross-linking of high affinity immunoglobulin E receptors (FcεRI), compared with those of the non-selective β-adrenoceptor agonist, isoproterenol (R-isomer), the selective β 2-adrenoceptor agonist, salbutamol (racemate), and the selective and long-acting β 2-adrenoceptor agonist, formoterol (racemate). We also evaluated the effect of S1319 on the intracellular cAMP level, inositol phosphate production and protein tyrosine phosphorylation in HCMC.¶Results: S1319 and β-adrenoceptor agonists inhibited the IgE-mediated release of tryptase. Approximate IC50 values of S1319, formoterol, isoproterenol and albuterol for the inhibition of tryptase release were 0.51 ± 0.12, 0.15 ± 0.1, 0.80 ± 0.09, and 28 ± 32.4 nM, respectively. S1319 and β-adrenoceptor agonists also inhibited TNF-α production by HCMC in a concentration-dependent manner. Approximate IC50 values of S1319, formoterol and isoproterenol for the inhibition of TNF-α production were 0.19 ± 0.03, 0.28 ± 0.02 and 0.32 ± 0.03 nM, respectively. S1319 caused a concentration-dependent increase in total cell cyclic AMP levels in HCMC. On the other hand, S1319 inhibited the accumulation of inositol 1,4,5-triphosphate and IgE-mediated protein tyrosine phosphorylation of 42-kDa protein, p42 mitogen activated protein (MAP) kinase (ERK-2).¶Conclusion: These results indicate that S1319 and β-adrenoceptor agonists are potent inhibitors of the IgE-mediated release of mediators from HCMC.
    Type of Medium: Electronic Resource
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