Fig. 6.
Genetic deletion of RSK2 significantly alters the relative rank order efficacy of 5-HT2A agonists: evidence for functional selectivity between WT and RSK2 KO MEFs. A, relative rank orders of efficacy (Emax, 5-HT set to 100%) were significantly altered between WT (■) and RSK2 KO MEFs (
) for 5-HT2A-mediated IP accumulation. Statistical ranking of relative Emax values was performed via one-way ANOVA and Tukey-Kramer multiple comparison post-tests in which agonists were assigned to statistically homogeneous groups (designated “a” through “f” in Table 4, labeled bars). Significant differences in rank order were denoted by changes in group membership, and agonists with nonoverlapping group assignments were considered to be significantly different. Values represent the mean of four to five independent experiments performed in duplicate. B, the relative efficacies of α-Me-5-HT, 5-methoxy-DMT, and DOI were reversed between WT (■) and RSK2 KO MEFs () for 5-HT2A-mediated IP accumulation (∗, statistically different from α-Me-5-HT, p < 0.05). Labeled bars represent statistically homogeneous groups (designated “a” through “f” in Table 4). C, concentration-response curves showing the relative abilities of α-Me-5-HT (■), 5-methoxy-DMT (○), and DOI (▴) to stimulate IP accumulation via 5-HT2A receptors in WT MEFs. Relative Emax values were significantly different between α-Me-5-HT and both 5-methoxy-DMT and DOI (p < 0.05). Values represent the mean ± S.E.M. of four to five independent experiments performed in duplicate. D, concentration-response curves showing the relative abilities of α-Me-5-HT (■), 5-methoxy-DMT (○), and DOI (▴) to stimulate IP accumulation via 5-HT2A receptors in RSK2 KO MEFs. Relative Emax values were significantly different between α-Me-5-HT and both 5-methoxy-DMT and DOI (p < 0.05). Values represent the mean ± S.E.M. of four to five independent experiments performed in duplicate.