VASOACTIVE-INTESTINAL-PEPTIDE AND PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE POTENTIATE C-FOS EXPRESSION INDUCED BY GLUTAMATE IN CULTURED CORTICAL-NEURONS

Previous reports have demonstrated that glutamate stimulates c-fos mRN A expression in primary cultures of mouse cerebral cortical neurons. W e show here that vasoactive intestinal peptide (VIP) induces c-fos mRN A expression; however, this effect of VIP is completely inhibited by t he noncompetitive NMDA receptor antagonist MK-801, therefore indicatin g that VIP stimulates c-fos expression in a glutamate-dependent manner . A similar effect was observed with pituitary adenylate cyclase-activ ating polypeptide27 (PACAP27). At the intracellular level, coactivatio n of protein kinases A and C mediates the glutamate-dependent stimulat ion of c-fos expression evoked by VIP, because either H-89 or staurosp orin inhibits the effect of VIP as well as that of glutamate. These re sults point to a ''biochemical AND gate'' mechanism, which implies the obligatory activation of both protein kinases A and C in the transduc tion of c-fos expression. In summary, this article provides evidence t hat VIP and PACAP27 potentiate the effect of glutamate, the principal effector on c-fos expression, suggesting that both peptides can increa se the ''throughput'' or ''strength'' of glutamate-containing circuits in the cerebral cortex.