Effect of lactisole on Tas1r3 variants. (a, b) Responses of cells co-transfected with rTas1r2 and rTas1r3 mutants to stimulation with 1 mM stevioside. (c) Calcium responses of cells co-transfected with rTas1r2 and the rTas1r3-V738A receptor variant to stimulation with various sweeteners in the presence and absence of lactisole. c, response of mock-transfected control cells; lac, 1.0 mM lactisole; asp, 15 mM aspartame; cyc, 30 mM cyclamate; neo, 0.1 mM neohesperidine dihydrochalcone; sac, 10 mM saccharin; suc, 100 mM sucrose; stev, 1 mM stevioside; -, response without lactisole; +, response in the presence of 1.0 mM lactisole. All sweeteners were used at concentrations which were close to the maximal obtainable signal. (d) Concentration-dependent inhibition of calcium responses by lactisole in cells transfected with hTAS1R2-hTAS1R3 (open circles, solid line), rTas1r2-rTas1r3 V738A (squares, dash-dot-dotted line), rTas1r2-rTas1r3 m6 (open triangles up, long dashed line), rTas1r2-rTas1r3 m6/1 (filled circles, short dashed line), rTas1r2-rTas1r3 m6/2 (triangles down, medium dashed line) or rTas1r2-rTas1r3 m6/3 (open diamond, dotted line) that were challenged with 3 mM stevioside.