Fig. 4
IL-1 receptor, Src, and GluN2B-mediated activation of p38 leads to the alterations in membrane expression and phosphorylation of the GluA2 but not of the GluA1 subunit in hyperammonemic rats. IL-1Ra, PP2, SB239063, an inhibitor of p38 MAP-kinase, or ifenprodil, an antagonist of GluN2B-containing NMDA receptors, were added to hippocampal slices. Phosphorylation of p38 (a, b, c), GluA1 at Ser831 (g), and GluA2 at Ser880 (e) and membrane expression of GluA1 (f) and GluA2 (d) subunits were analyzed as described in the “Methods” section. Values are expressed as percentage of basal levels in control rats and are the mean ± SEM of 18, 16, 20, 30, 17, 22, and 29 rats per group in a, b, c, d, e, f, and g respectively. Data were analyzed by two-way ANOVA. In a, F (1, 66) = 0.004793 for effect of HA, p = 0.9450; F (1, 66) = 23.42 for effect of IL-1Ra, p < 0.0001; and F (1, 66) = 6.695 for interaction, p = 0.0119. In b, F (1, 59) = 0.02867 for effect of HA, p = 0.8661; F (1, 59) = 6.959 for effect of PP2, p = 0.0106; and F (1, 59) = 4.611 for interaction, p = 0.0359. In c, F (1, 76) = 2.894 for effect of HA, p = 0.0930; F (1, 76) = 7.961 for effect of ifenprodil, p = 0.0061; and F (1, 76) = 1.682 for interaction, p = 0.1985. In d, F (1, 116) = 4.486 for effect of HA, p = 0.0363; F (1, 116) = 7.577 for effect of SB239063, p = 0.0069; and F (1, 116) = 2.616 for interaction, p = 0.1085. In e, F (1, 64) = 0.2959 for effect of HA, p = 0.5883; F (1, 64) = 26.34 for effect of SB239063, p < 0.0001; and F (1, 64) = 10.08 for interaction, p = 0.0023. In f, F (1, 83) = 0.006480 for effect of HA, p = 0.9360; F (1, 83) = 0.1665 for effect of SB239063, p = 0.6843; and F (1, 83) = 2.228 for interaction, p = 0.1393. In g, F (1, 110) = 6.864 for effect of HA, p = 0.0100; F (1, 110) = 0.9431 for effect of SB239063, p = 0.3336; and F (1, 110) = 0.001793 for interaction, p = 0.9663. Values significantly different from control rats are indicated by asterisk and from hyperammonemic rats are indicated by “a”. Bonferroni post-test: *p < 0.05, ***p < 0.001, ap < 0.05, aap < 0.01, aaap < 0.001