Fig. 4
FFAR1 agonists manifest a broncho-protective effect in β2AR-desensitized HASM cells. HASM cells were desensitized by salmeterol (1 µM) for 18 h. Then, HASM cells pre-treated with vehicle (DMSO), GW9508 (10 µM), or TAK875 (10 µM) for 30 min, then stimulated with carbachol 25 µM for 10 min. Agonists-induced MLC phosphorylation were determined. a, b Isoproterenol decreased CCh-induced MLC phosphorylation, but it loses its bronchoprotective effects after salmeterol-induced β2AR desensitization. (n = 6 donors) c, d FFAR1 agonist TAK875 attenuated CCh-induced MLC phosphorylation in β2AR desensitized HASM cells. (n = 6 donors) e FFAR1 agonists have little effect on cyclic AMP production in HASM cells. HASM cells pre-treated with vehicle (DMSO), GW9508 (10 µM), or TAK875 (10 µM) for 30 min, then stimulated with or without isoproterenol for 5 min to induce cAMP production. Baseline and iso-induced cAMP levels were determined (n = 6 donors). (One-way ANOVA with Dunnett’s Test, compared to Veh; p < 0.01: **; ns not significant, NT no treatment)