Figure 5.

Concomitant activation of astrocytic AMPARs and mGluRs results in a Ca²⁺and protein kinase C-dependent increase in TACE-like activity. A, Coactivation of AMPARs and mGluRs with AMPA plus tACPD (at 100 μm each) results in a sustained increase in intracellular Ca²⁺ levels, determined in monolayers of hypothalamic astrocytes loaded with fura-2 AM. B, TACE-like activity is also increased when AMPA and ACPD are administrated together, and this increase is prevented by TAPI-2, a selective TACE inhibitor. C, The increase in astrocytic TACE-like activity induced by AMPA plus tACPD is inhibited by sequestering either extracellular or intracellular Ca²⁺ with the chelating agents EGTA and BAPTA-AM, respectively (each agent at 1 μm); glutamate receptor agonist-induced TACE-like activity is prevented by inhibiting protein kinase C with H7. In B, p < 0.001 untreated and AMPA or tACPD only versus AMPA plus ACPD and AMPA plus ACPD plus TAPI. In C,**p < 0.01 versus control group; ^#p < 0.05 and ^##p < 0.01 versus AMPA plus ACPD group (n = 6–8 independent observations per group). RFU, Relative fluorescence units.