AMPLIFICATION OF CALCIUM-INDUCED GENE-TRANSCRIPTION BY NITRIC-OXIDE IN NEURONAL CELLS

NITRIC oxide (NO) is a short-lived, highly reactive gas, which has bee n identified as a mediator in vasodilation, an active agent in macroph age cytotoxicity and neurotoxicity, and a neurotransmitter in the cent ral and peripheral nervous systems1-5. Production of NO by neurons is critical for facilitated synaptic transmission in models of synaptic p lasticity such as long-term potentiation and long-term depression, sug gesting a role for NO as a retrograde messenger that could complete a hypothetical feed-back loop by strengthening the connection between po stsynaptic and presynaptic cells6-10. We report here that although alo ne NO has no evident effect on transcription, it can act as an amplifi er of calcium signals in neuronal cells. NO and Ca2+ action have to co incide in time for amplification to occur. Experiments with a series o f simplified reporter genes in combination with specific recombinant p rotein kinase inhibitors suggest that induction of gene activity follo wing NO-amplified calcium action involves protein kinase A-dependent a ctivation of the transcription factor CREB.