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An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation

Schuman, Erin M. and Meffert, Mollie K. and Schulman, Howard and Madison, Daniel V. (1994) An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation. Proceedings of the National Academy of Sciences of the United States of America, 91 (25). pp. 11958-11962. ISSN 0027-8424. PMCID PMC45355.

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Recent studies of long-term potentiation (LTP) in the CA1 region of the hippocampus have demonstrated that nitric oxide (NO) may be involved in some forms of LTP and have suggested that postsynaptically generated NO is a candidate to act as a retrograde messenger. However, the molecular target(s) of NO in LTP remain to be elucidated. The present study examined whether either of two potential NO targets, a soluble guanylyl cyclase or an ADP-ribosyltransferase (ADPRT; EC plays a role in LTP. The application of membrane-permeant analogs of cGMP did not produce any long-lasting alterations in synaptic strength. In addition, application of a cGMP-dependent protein kinase inhibitor did not prevent LTP. We found that the CA1 tissue from hippocampus possesses an ADPRT activity that is dramatically stimulated by NO and attenuated by two different inhibitors of mono-ADPRT activity, phylloquinone and nicotinamide. The extracellular application of these same inhibitors prevented LTP. Postsynaptic injection of nicotinamide failed to attenuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus. These results suggest that ADP-ribosylation plays a role in LTP and are consistent with the idea that an ADPRT may be a target of NO action.

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URLURL TypeDescription CentralArticle
Schuman, Erin M.0000-0002-7053-1005
Additional Information:© 1994 by the National Academy of Sciences. Communicated by De-Pei Feng, July 28, 1994 (received for review May 27, 1994). We thank J. Kauer, R. Mooney, B. Premack, and F. Schweizer for helpful comments and discussion. D.V.M. is a Lucille P. Markey Scholar. This work was supported by the Lucille P. Markey Charitable Trust, a National Institute of Mental Health Silvio Conte Center for Neuroscience grant (48108, to H.S. and D.V.M.) and National Institutes of Health Grant 2F32NS08934 (to E.M.S.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
Lucille P. Markey Charitable TrustUNSPECIFIED
NIHMH 48108
NIH Postdoctoral Fellowship2F32NS08934
Issue or Number:25
PubMed Central ID:PMC45355
Record Number:CaltechAUTHORS:SCHpnas94
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1507
Deposited By: Tony Diaz
Deposited On:25 Jan 2006
Last Modified:04 Jun 2020 19:54

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