AN ADP-RIBOSYLTRANSFERASE AS A POTENTIAL TARGET FOR NITRIC-OXIDE ACTION IN HIPPOCAMPAL LONG-TERM POTENTIATION

Recent studies of long-term potentiation (LTP) in the CA1 region of th e hippocampus have demonstrated that nitric oxide (NO) may be involved in some forms of LTP and have suggested that postsynaptically generat ed NO is a candidate to act as a retrograde messenger. However, the mo lecular target(s) of NO in LTP remain to be elucidated. The present st udy examined whether either of two potential NO targets, a soluble gua nylyl cyclase or an ADP-ribosyltransferase (ADPRT; EC 2.4.2.31) plays a role in LTP, The application of membrane-permeant analogs of cGMP di d not produce any long-lasting alterations in synaptic strength. In ad dition, application of a cGMP-dependent protein kinase inhibitor did n ot prevent LTP. We found that the CA1 tissue from hippocampus possesse s an ADPRT activity that is dramatically stimulated by NO and attenuat ed by two different inhibitors of mono-ADPRT activity, phylloquinone a nd nicotinamide. The extracellular application of these same inhibitor s prevented LTP. Postsynaptic injection of nicotinamide failed to atte nuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus. These results suggest that ADP-ribosylati on plays a role in LTP and are consistent with the idea that an ADPRT may be a target of NO action.