The effects of S1319, a novel marine sponge-derived beta(2)-adrenoceptor agonist, on IgE-mediated activation of human cultured mast cells

Objective: This study aimed to evaluate the ability of S1319 (4-hydroxy-7-[ 1-(1-hydroxy-2-methylamino) ethyl]-1,3-benzothiazol-2(3H)-one acetate), a n ovel beta(2),adrenoceptor selective agonist derived from marine sponge, to inhibit IgE-mediated activation of human cultured mast cells (HCMC) in vitr o. Materials and Methods: We examined the effect of S1319 (racemate) on trypta se release and tumor necrosis factor-alpha (TNF-alpha) production in HCMC g enerated from human cord blood cells, after cross-linking of high affinity immunoglobulin E receptors (Fc epsilon RI), compared with those of the nons elective beta(2)-adrenoceptor agonist, isoproterenol (R-isomer), the select ive beta(2)-adrenoceptor agonist, salbutamol (racemate), and the selective and long-acting beta(2)-adrenoceptor agonist, formoterol (racemate). We als o evaluated the effect of S1319 on the intracellular cAMP level, inositol p hosphate production and protein tyrosine phosphorylation in HCMC. Results: S1319 and beta(2)-adrenoceptor agonists inhibited the IgE-mediated release of tryptase. Approximate IC50 values of S1319, formoterol, isoprot erenol 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 a nd beta(2)-adrenoceptor agonists also inhibited TNF-alpha production by HCM C in a concentration-dependent manner. Approximate IC50 values of S1319, fo rmoterol and isoproterenol for the inhibition of TNF-alpha production were 0.19 +/- 0.03, 0.28 +/- 0.02 and 0.32 +/- 0.03 nM, respectively. S1319 caus ed a concentration-dependent increase in total cell cyclic AMP levels in HC MC. On the other hand, S1319 inhibited the accumulation of inositol 1,4,5-t riphosphate and IgE-mediated protein tyrosine phosphorylation of 42-kDa pro tein, p42 mitogen activated protein (MAP) kinase (ERK-2). Conclusion: These results indicate that S1319 and beta(2)-adrenoceptor agon ists are potent inhibitors of the IgE-mediated release of mediators from HC MC.