Cross-talk between β-adrenergic and metabotropic glutamate receptors in rat C6 glioma cells

Exposure of rat C6 glioma cells to the β-adrenergic receptor agonist isoproterenol potentiates basal and metabotropic glutamate receptor-stimulated phospholipase C activity in rat C6 glioma cells. After treatment of cells for 24 h with 10 μM isoproterenol, metabotropic glutamate receptors and phospholipase C activity were determined in C6 plasma membranes. Isoproterenol treatment caused an increase of 67% in the total number of binding sites (B_max=12.1±1.8 pmol/mg protein versus B_max=20.27±0.88 pmol/mg protein) with K_d values of the same order (K_d=1250±101 nM versus K_d=1401±211 nM), using l-[³H]glutamate as radioligand. On the other hand, basal, guanylyl imidodiphosphate (Gpp[NH]p)- and trans-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD)-stimulated phospholipase C activities were also significantly increased in membranes from isoproterenol-treated cells compared to control cells, by 337%, 33% and 40% respectively. Moreover, a significant increase of 94% in the steady-state level of phospholipase C β₁ in membranes from isoproterenol-treated cells compared to control was also detected by immunoblot. These results show that metabotropic glutamate receptors and its effector system, phospholipase C, are affected by isoproterenol treatment, showing the existence of cross-talk between these signal transduction pathways.