Abstract
Nitric oxide (NO) is involved in hippocampal phenomena of synaptic plasticity. The present microdialysis study investigated a possible role of NO and of endothelial NO synthase (eNOS) activity in the control of hippocampal acetylcholine (ACh) release. 3-Morpholinosydnonimine (SIN-1), an NO donor, stimulated ACh release by 50%–70% when infused into the hippocampus of wild type C57B16 mice. Infusion of l-nitroarginine (L-NA), a broad-spectrum inhibitor of NO synthases, decreased hippocampal ACh efflux by approximately 50%. Mice lacking eNOS (eNOS knockouts) had identical basal effluxes of hippocampal ACh as wild type mice, and the responses to SIN-1 and L-NA were unchanged in the absence of eNOS activity. We conclude that nitric oxide (NO) stimulates hippocampal ACh release in a tonic fashion, but independently of eNOS activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Garthwaite, J. and Boulton, C. L. 1995. Nitric oxide signaling in the central nervous system. Ann. Rev. Physiol. 57:683–706.
Kiss, J. P. and Vizi, S. 2001. Nitric oxide: A novel link between synaptic and nonsynaptic transmission. Trends Neurosci. 24: 211–215.
Iadecola, C. 1997.Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci. 20:132–139.
Hölscher, C. 1997. Nitric oxide, the enigmatic neuronal messenger: Its role in synaptic plasticity. Trends Neurosci. 20: 298–303.
Law, A., Gauthier, S., and Quirion, R. 2001. Say NO to Alzheimer's disease: The putative links between nitric oxide and dementia of the Alzheimer's type. Brain Res. Rev. 35:73–96.
Tran, M. H., Yamada, K., Olariu, A., Mizuno, M., Ren, X. H., and Nabeshima, T. 2001. Amyloid β-peptide induces nitric oxide production in rat hippocampus: Association with cholinergic dysfunction and amelioration by inducible nitric oxide synthase inhibitors. FASEB J. (April 6, 2001) 10.1096/fj.00-0719fje.
O'Dell, T. J., Huang, P. L., Dawson, T. M., Dinerman, J. L., Snyder, S. H., Kandel, E. R., and Fishman, M. C. 1994. Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS. Science 265:542–546.
Son, H., Hawkins, R. D., Martin, K., Kiebler, M., Huang, P. L., Fishman, M. C., and Kandel, E. R. 1996. Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell 87:1015–1023.
Kantor, D. B., Lanzrein, M., Stary, S. J., Sandoval, G. M., Smith, W. B., Sullivan, B. M., Davidson, N., and Schuman, E. M. 1996. A role for endothelial NO synthase in LTO revealed by adenovirus-mediated inhibition and rescue. Science 274: 1744–1748.
Wilson, R. I., Godecke, A., Brown, R. E., Schrader, J., and Haas, H. L. 1999. Mice deficient in endothelial nitric oxide synthase exhibit a selective deficit in hippocampal long-term potentiation. Neuroscience 90:1157–1165.
Suzuki, T., Nakajima, K., Fujimoto, K., Fujii, T., and Kawashima, K. 1997. Nitric oxide increases stimulation-evoked acetylcholine release from rat hippocampal slices by a cyclic GMP-independent mechanism. Brain Res. 760:158–162.
Prast, H., Fischer, H., Werner, E., Werner-Felmayer, G., and Philippu, A. 1995. Nitric oxide modulates the release of acetylcholine in the ventral striatum of the freely moving rat. Naunyn Schmiedebergs Arch. Pharmacol. 352:67–73.
Prast, H., Tran, M. H., Fischer, H., and Philippu, A. 1998. Nitric oxide-induced release of acetylcholine in the nucleus accumbens: Role of cyclic GMP, glutamate, and GABA. J. Neurochem. 71:266–273.
Leonard, T. O. and Lydic, R. 1995. Nitric oxide synthase inhibition decreases pontine acetylcholine release. Neuroreport 6: 1525–1529.
Erb, C., Troost, J., Kopf, S., Schmitt, U., Löffelholz, K., Soreq, H., and Klein, J. 2001. Compensatory mechanisms enhance hippocampal acetylcholine release in transgenic mice expressing human acetylcholinesterase. J. Neurochem. 77:638–646.
Kopf, S. R., Buchholzer, M. L., Hilgert, M., Löffelholz, K., and Klein, J. 2001. Glucose plus choline improve passive avoidance behaviour and increase hippocampal acetylcholine release in mice. Neuroscience 103:365–371.
Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., and Fishman, M. C. 1995. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377:239–242.
Franklin, K. B. J. and Paxinos, G. 1997. The mouse brain in stereotaxic coordinates, Academic Press, San Diego.
Arancio, O., Kiebler, M., Lee, C. J., Lev-Ram, V., Tsien, R. Y., Kandel, E. R., and Hawkins, R. D. 1996. Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 87:1025–1035.
Hirsch, D. B., Steiner, J. P., Dawson, T. M., Mammen, A., Hayek, E., and Snyder, S. H. 1993. Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes. Curr. Biol. 3:749–754.
Kano, T., Shimizu-Sasamata, M., Huang, P. L., Moskowitz, M. A., and Lo, E. H. 1998. Effects of nitric oxide synthase gene knockout on neurotransmitter release in vivo. Neuroscience 86: 695–699.
Förstermann, U., Gath, I., Schwarz, P., Closs, E. I., and Kleinert, H. 1995. Isoforms of nitric oxide synthase. Biochem. Pharmacol. 50:1321–1332.
Kraus, M. M. and Prast, H. 2001. The nitric oxide system modulates the in vivo release of acetylcholine in the nucleus accumbens induced by stimulation of the hippocampal fornix/fimbria-projection. Eur. J. Neurosci. 14:1105–1112.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Buchholzer, ML., Klein, J. Nitrergic Modulation of Hippocampal Acetylcholine Release Is Independent of Endothelial NO Synthase Activity. Neurochem Res 28, 587–591 (2003). https://doi.org/10.1023/A:1022885726287
Issue Date:
DOI: https://doi.org/10.1023/A:1022885726287