Effects of t-ACPD on neural survival and second messengers in cultured cerebral cortical neurones

The cytotoxic potential of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (t-ACPD) in cultured murine cerebral cortical neurones was examined. Exposure to t-ACPD (1 mM, 16 h) did not induce cytotoxicity per se or affect N-methyl-D-aspartate-induced toxicity. Phosphoinositide hydrolysis was weakly stimulated by t-ACPD (1 mM), while no alteration of intracellular calcium levels was observed after exposure to 1 mM t-ACPD. However, forskolin-stimulated cAMP formation was inhibited by t-ACPD (IC50 = 8 +/- 2 microM) with a maximal inhibition of 36 +/- 4% of control levels. These data suggest that the lack of neurotoxic effects of t-ACPD may be related to the negligible efficacy of t-ACPD to activate mGluRs coupled to the IP3/Ca(2+)-cascade and/or putative counteracting effects of t-ACPD mediated by mGluRs negatively coupled to the cAMP-cascade.