Figure 2: Exemestane (EXE), letrozole (LTZ) and anastrozole (ANA) selectively activate the native TRPA1 channel expressed in rodent dorsal root ganglion (DRG) neurons.
(a) Representative traces of calcium response evoked by EXE (100 μM), LTZ (100 μM), ANA (300 μM) in cultured rat DRG neurons, which also respond to allyl isothiocyanate (AITC; 30 μM) and capsaicin (CPS; 0.1 μM). Calcium responses evoked by AIs and AITC are abolished by the selective TRPA1 antagonist, HC-030031 (HC; 30 μM), which does not affect response to CPS. (b) Concentration-response curves of EXE, LTZ and ANA, yielded EC50 (95% confidence interval) of 82 (61–108) μM, 78 (39–152) μM, and 135 (78–231) μM, respectively. (c) Calcium responses induced by AIs are inhibited by HC and unaffected by the TRPV1 antagonist, capsazepine (CPZ; 10 μM). §P<0.05 versus Veh, *P<0.05 versus EXE, LTZ or ANA; ANOVA and Bonferroni post hoc test. (d) Representative traces and (e) pooled data of the calcium response evoked by EXE, LTZ, ANA (all 100 μM) or AITC (30 μM), in neurons isolated from Trpa1+/+ mice. Neurons isolated from Trpa1−/− mice do not respond to AITC, EXE, LTZ and ANA, whereas they do respond normally to CPS (0.1 μM). In DRG neurons isolated from both Trpa1+/+ and Trpa1−/− mice, calcium response is evaluated only in capsaicin responding neurons. §P<0.05 versus Veh, *P<0.05 versus EXE, LTZ, ANA or AITC-Trpa1+/+, ANOVA and Bonferroni post hoc test. Veh is the vehicle of AIs; dash (-) indicates the combination of the vehicles of HC and CPZ. Each point or column represents the mean±s.e.m. of at least 25 neurons obtained from 3 to 7 independent experiments.
