Figure 2
Xanthurenic acid (XA) activates mGlu2/3 receptor signaling in heterologous expression systems and brain tissue.
(A) Left: concentration-dependent inhibition of forskolin-stimulated cAMP formation by XA in HEK293 cells expressing mGlu2 receptors. Values are means + S.D. of 2–5 determinations. *p < 0.05 vs. forskolin alone (One-way ANOVA + Fisher’s LSD; F(8,24) = 5.8). Right: inhibition of forskolin-stimulated cAMP formation by 2R,4R-APDC or XA in the absence or presence of LY341495. Values (means + S.E.M.; n = 4) were extrapolated from a different experiment with additional groups not shown here. p < 0.05 vs. forskolin alone (*) or vs. forskolin + 2R,4R-APDC or forskolin + XA (#) (One-way ANOVA + Fisher’s LSD; F(11,36) = 22.326). (B) Left and Right: same as in (A), but in mGlu3-expressing HEK293 cells. Left: values are means + S.D. of 2–3 determinations. *p < 0.05 vs. forskolin alone (One-way ANOVA + Fisher’s LSD; F(8,25) = 10.49). Right: values (means + S.D.; n = 4) were extrapolated from a different experiment with additional groups not shown here. p < 0.05 vs. forskolin alone (*) or vs. forskolin + 2R,4R-APDC or forskolin + XA (#) (One-way ANOVA + Fisher’s LSD; F(11,36) = 26.913). XA (30 or 300 μM) had no effect on cAMP in the absence of forskolin in both (A,B). (C–E) XA fails to inhibit forskolin-stimulated cAMP formation in mGlu4- and mGlu7-expressing cells or in mock cells. Values are means + S.D. of 4 determinations. *p < 0.05 vs. forskolin alone (One-way ANOVA + Fisher’s LSD; (C) F(8,26) = 18.36; (D) F(4,19) = 12.03. (F) Inhibition of cAMP formation by XA or LY379268 in cortical slices prepared from wild-type and mGlu2−/− mice. Values are means + S.D. of 4 determinations; p < 0.05 vs. the respective control values (*) or vs. the respective values obtained in the absence of LY341495 (#). (One-way ANOVA + Fisher’s LSD; wild-type mice: F(7,21) = 4.885; mGlu2−/− mice: F(5,14) = 4.478. (G) Stimulation of PI hydrolysis in cortical slices incubated in the absence or presence of DHPG, XA, or LY379268. Values are means + S.D. of 4–5 determinations; p < 0.05 vs. basal values of the control group (*) or the DHPG group (#) (One-way ANOVA + Fisher’s LSD; F(7,25) = 24.663.
