Intracellular cAMP regulates the response to NMDA in hippocampal neurons.

We have studied the effects of intracellular cyclic AMP (cAMP) on the response to N-methyl-D-aspartate (NMDA) in hippocampal cultured neurons by loading them with 2'-o-dibutyryladenosine 3', 5'-cyclic monophosphate (dcAMP) and have obtained evidence for regulation of Ca2+ release from intracellular stores by cAMP. Extracellular Ringer's solution was either Ca(2+)-containing or Ca(2+)-free. A brief initial stimulation with NMDA (10-100 microM, 12 s) was required before the neurons were loaded with dcAMP to potentiate the changes in intracellular Ca2+ concentration induced by the second stimulus of NMDA. Forskolin (10 microM) mimicked dcAMP, but to a lesser extent. A phorbol ester 12-o-tetradecanoylphorbol-13-acetate (100 nM) inhibited the effect of dcAMP.