Skip to main content
. 2013 Sep 4;305(9):R1040–R1050. doi: 10.1152/ajpregu.00296.2013

Fig. 2.

Fig. 2.

Compound 5 effectively inhibits TRPM8 activity in vivo. A: effects of compound 5 treatment on core temperature of conscious wild-type mice exposed to mild cooling (18°C). Mice were held at 18°C for 30 min, then briefly removed from the chamber, injected with compound 5 (n = 7) or vehicle (n = 7) and exposed to mild cooling at 18°C for an additional 2 h. Compound 5 treatment led to a statistically significant decrease in core temperature during 5–120 min of the cold exposure [two-way repeated-measures ANOVA, effect of the treatment group: F(1,12) = 14.646, P = 0.002; Holm-Sidak test for the effect of the treatment group within 5–120-min timepoints, *P < 0.05]. B: wild-type mice pretreated with vehicle (Veh, n = 5) or compound 5 (Comp5, n = 5) 60 min earlier, as well as TRPM8 KO mice (TRPM8 KO, n = 5), were injected with TRPM8 agonist icilin (20 mg/kg ip). The number of icilin-induced behaviors, counted during the 10th min posti-icilin (equal to 70th min after administration of compound 5), in mice pretreated with compound 5 was significantly lower compared with vehicle-treated mice and not different compared with TRPM8 KO mice. One-way ANOVA across three groups, F(2,12) = 26.78, P < 0.001. Student-Newman-Keuls post hoc test: *P < 0.001 for Veh vs. Comp5 and Veh vs. TRPM8 KO; P = 0.568 (not significant, n.s.) for Comp5 vs. TRPM8 KO. C: effects of compound 5 treatment on cold sensitivity of mice in the temperature preference assay. Wild-type mice (WT, n = 8), as well as TRPM8 KO mice (M8KO, n = 9) were pretreated with vehicle (Veh) or compound 5 (Comp5) 60 min earlier and then allowed to explore the contiguous surface, two sides of which had cold (22°C) or warm (30°C) temperature, for 6 min. The percentage of time spent on each side was determined. The percentage of time spent on the cold side by compound 5-treated WT mice was significantly higher compared with vehicle-treated WT mice and not different from vehicle-treated M8KO mice. There was no increase in time on the cold side in compound 5-treated M8KO above that in vehicle-treated M8KO mice. One-way ANOVA across four groups, F(3,30) = 5.52, P = 0.004. Student-Newman-Keuls post hoc test: *P < 0.01 for WT Veh vs. WT Comp5, M8KO Veh, and M8KO Comp5 each; P > 0.05 (n.s.) for WT Comp5, M8KO Veh, and M8KO Comp5 pairwise.