NO/cGMP-Dependent Modulation of Synaptic Transmission

  • Robert Feil
  • Thomas Kleppisch
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 184)

Nitric oxide (NO) is a multifunctional messenger in the CNS that can signal both in antero- and retrograde directions across synapses. Many effects of NO are mediated through its canonical receptor, the soluble guanylyl cyclase, and the second messenger cyclic guanosine-3′,5′-monophosphate (cGMP). An increase of cGMP can also arise independently of NO via activation of membrane-bound particulate guanylyl cyclases by natriuretic peptides. The classical targets of cGMP are cGMP-dependent protein kinases (cGKs), cyclic nucleotide hydrolysing phosphodiesterases, and cyclic nucleotide-gated (CNG) cation channels. The NO/cGMP/cGK signalling cascade has been linked to the modulation of transmitter release and synaptic plasticity by numerous pharmacological and genetic studies. This review focuses on the role of NO as a retrograde messenger in long-term potentiation of transmitter release in the hippocampus. Presynaptic mechanisms of NO/cGMP/cGK signalling will be discussed with recently identified potential downstream components such as CaMKII, the vasodilator-stimulated phosphoprotein, and regulators of G protein signalling. NO has further been suggested to increase transmitter release through presynaptic clustering of a-synuclein. Alternative modes of NO/cGMP signalling resulting in inhibition of transmitter release and long-term depression of synaptic activity will also be addressed, as well as anterograde NO signalling in the cerebellum. Finally, emerging evidence for cGMP signalling through CNG channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels will be discussed.


Nitric Oxide Transmitter Release Guanylyl Cyclase Retrograde Messenger Schaffer Collateral Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abudara V, Alvarez AF, Chase MH, Morales FR (2002) Nitric oxide as an anterograde neurotransmitter in the trigeminal motor pool. J Neurophysiol 88:497-506PubMedGoogle Scholar
  2. Ajima A, Ito M (1995) A unique role of protein phosphatases in cerebellar long-term depression. Neuroreport 6:297-300PubMedCrossRefGoogle Scholar
  3. Antonova I, Arancio O, Trillat AC, Wang HG, Zablow L, Udo H, Kandel ER, et al. (2001) Rapid increase in clusters of presynaptic proteins at onset of long-lasting potentiation. Science 294:1547-50PubMedCrossRefGoogle Scholar
  4. Arancio O, Kandel ER, Hawkins RD (1995) Activity-dependent long-term enhancement of transmitter release by presynaptic 3 ,5 -cyclic GMP in cultured hippocampal neurons. Nature 376:74-80PubMedCrossRefGoogle Scholar
  5. Arancio O, Kiebler M, Lee CJ, Lev-Ram V, Tsien RY, Kandel ER, Hawkins RD (1996) Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 87:1025-35PubMedCrossRefGoogle Scholar
  6. Arancio O, Antonova I, Gambaryan S, Lohmann SM, Wood JS, Lawrence DS, Hawkins RD (2001) Presynaptic role of cGMP-dependent protein kinase during long-lasting potentiation. J Neurosci 21:143-9PubMedGoogle Scholar
  7. Aswad DW, Greengard P (1981) A specific substrate from rabbit cerebellum for guanosine 3 ,5 monophosphate-dependent protein kinase. I. Purification and characterization. J Biol Chem 256:3487-93PubMedGoogle Scholar
  8. Barco A, Alarcon JM, Kandel ER (2002) Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell 108:689-703PubMedCrossRefGoogle Scholar
  9. Bear MF, Malenka RC (1994) Synaptic plasticity:LTP and LTD. Curr Opin Neurobiol 4:389-99PubMedCrossRefGoogle Scholar
  10. Bender RA, Brewster A, Santoro B, Ludwig A, Hofmann F, Biel M, Baram TZ (2001) Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus. Neuroscience 106:689-98PubMedCrossRefGoogle Scholar
  11. Betz WJ, Bewick GS (1992) Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255:200-3PubMedCrossRefGoogle Scholar
  12. Biel M, Zong X, Ludwig A, Sautter A, Hofmann F (1999) Structure and function of cyclic nucleotide-gated channels. Rev Physiol Biochem Pharmacol 135:151-71PubMedCrossRefGoogle Scholar
  13. Blackshaw S, Eliasson MJ, Sawa A, Watkins CC, Krug D, Gupta A, Arai T, et al. (2003) Species, strain and developmental variations in hippocampal neuronal and endothelial nitric oxide synthase clarify discrepancies in nitric oxide-dependent synaptic plasticity. Neuroscience 119:979-90PubMedCrossRefGoogle Scholar
  14. Boulton CL, Southam E, Garthwaite J (1995) Nitric oxide-dependent long-term potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase. Neuroscience 69:699-703PubMedCrossRefGoogle Scholar
  15. Boxall AR, Garthwaite J (1996) Long-term depression in rat cerebellum requires both NO synthase and NO-sensitive guanylyl cyclase. Eur J Neurosci 8:2209-12PubMedCrossRefGoogle Scholar
  16. Bradley J, Zhang Y, Bakin R, Lester HA, Ronnett GV, Zinn K (1997) Functional expression of the heteromeric “olfactory” cyclic nucleotide-gated channel in the hippocampus: a potential effector of synaptic plasticity in brain neurons. J Neurosci 17:1993-2005PubMedGoogle Scholar
  17. Bradley J, Frings S, Yau KW, Reed R (2001) Nomenclature for ion channel subunits. Science 294:2095-6PubMedCrossRefGoogle Scholar
  18. Bredt DS, Snyder SH (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682-5PubMedCrossRefGoogle Scholar
  19. Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, et al. (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains. Cell 84:757-67PubMedCrossRefGoogle Scholar
  20. Broillet MC, Firestein S (1996) Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron 16:377-85PubMedCrossRefGoogle Scholar
  21. Broillet MC, Firestein S (1997) Beta subunits of the olfactory cyclic nucleotide-gated channel form a nitric oxide activated Ca2+ channel. Neuron 18:951-8PubMedCrossRefGoogle Scholar
  22. Bugnon O, Schaad NC, Schorderet M (1994) Nitric oxide modulates endogenous dopamine release in bovine retina. Neuroreport 5:401-4PubMedCrossRefGoogle Scholar
  23. Burkhardt M, Glazova M, Gambaryan S, Vollkommer T, Butt E, Bader B, Heermeier K, et al. (2000) KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial cells. J Biol Chem 275:33536-41PubMedCrossRefGoogle Scholar
  24. Chetkovich DM, Klann E, Sweatt JD (1993) Nitric oxide synthase-independent long-term potentiation in area CA1 of hippocampus. Neuroreport 4:919-22PubMedCrossRefGoogle Scholar
  25. Chien WL, Liang KC, Teng CM, Kuo SC, Lee FY, Fu WM (2005) Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1. Eur J Neurosci 21:1679-88PubMedCrossRefGoogle Scholar
  26. Christopherson KS, Hillier BJ, Lim WA, Bredt DS (1999) PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J Biol Chem 274:27467-73PubMedCrossRefGoogle Scholar
  27. Chung HJ, Steinberg JP, Huganir RL, Linden DJ (2003) Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. Science 300:1751-5PubMedCrossRefGoogle Scholar
  28. Clementi E, Sciorati C, Riccio M, Miloso M, Meldolesi J, Nistico G (1995) Nitric oxide action on growth factor-elicited signals. Phosphoinositide hydrolysis and [Ca2+]i responses are negatively modulated via a cGMP-dependent protein kinase I pathway. J Biol Chem 270:22277-82PubMedCrossRefGoogle Scholar
  29. Collin T, Marty A, Llano I (2005) Presynaptic calcium stores and synaptic transmission. Curr Opin Neurobiol 15:275-81PubMedCrossRefGoogle Scholar
  30. Dang MT, Yokoi F, Yin HH, Lovinger DM, Wang Y, Li Y (2006) Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum. Proc Natl Acad Sci USA 103:15254-9PubMedCrossRefGoogle Scholar
  31. Daniel H, Levenes C, Crepel F (1998) Cellular mechanisms of cerebellar LTD. Trends Neurosci 21:401-7PubMedCrossRefGoogle Scholar
  32. Dawson TM, Dawson VL (1996) Nitric oxide synthase:role as a transmitter/mediator in the brain and endocrine system. Annu Rev Med 47:219-27PubMedCrossRefGoogle Scholar
  33. De Vente J, Asan E, Gambaryan S, Markerink-van Ittersum M, Axer H, Gallatz K, Lohmann SM, et al. (2001) Localization of cGMP-dependent protein kinase type II in rat brain. Neuroscience 108:27-49PubMedCrossRefGoogle Scholar
  34. De Zeeuw CI, Hansel C, Bian F, Koekkoek SK, van Alphen AM, Linden DJ, Oberdick J (1998) Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. Neuron 20:495-508PubMedCrossRefGoogle Scholar
  35. Demas GE, Kriegsfeld LJ, Blackshaw S, Huang P, Gammie SC, Nelson RJ, Snyder SH (1999) Elimination of aggressive behavior in male mice lacking endothelial nitric oxide synthase. J Neurosci 19:RC30PubMedGoogle Scholar
  36. DiCicco-Bloom E, Lelievre V, Zhou X, Rodriguez W, Tam J, Waschek JA (2004) Embryonic expression and multifunctional actions of the natriuretic peptides and receptors in the developing nervous system. Dev Biol 271:161-75PubMedCrossRefGoogle Scholar
  37. Dickie BG, Lewis MJ, Davies JA (1992) NMDA-induced release of nitric oxide potentiates aspartate overflow from cerebellar slices. Neurosci Lett 138:145-8PubMedCrossRefGoogle Scholar
  38. Dinerman JL, Dawson TM, Schell MJ, Snowman A, Snyder SH (1994) Endothelial nitric oxide synthase localized to hippocampal pyramidal cells:implications for synaptic plasticity. Proc Natl Acad Sci USA 91:4214-8PubMedCrossRefGoogle Scholar
  39. Ding JD, Burette A, Nedvetsky PI, Schmidt HH, Weinberg RJ (2004) Distribution of soluble guanylyl cyclase in the rat brain. J Comp Neurol 472:437-48PubMedCrossRefGoogle Scholar
  40. Doreulee N, Brown RE, Yanovsky Y, Godecke A, Schrader J, Haas HL (2001) Defective hippocampal mossy fiber long-term potentiation in endothelial nitric oxide synthase knockout mice. Synapse 41:191-4PubMedCrossRefGoogle Scholar
  41. El-Husseini AE, Bladen C, Vincent SR (1995) Molecular characterization of a type II cyclic GMPdependent protein kinase expressed in the rat brain. J Neurochem 64:2814-7PubMedGoogle Scholar
  42. El-Husseini AE, Williams J, Reiner PB, Pelech S, Vincent SR (1999) Localization of the cGMPdependent protein kinases in relation to nitric oxide synthase in the brain. J Chem Neuroanat 17:45-55PubMedCrossRefGoogle Scholar
  43. Eliasson MJ, Blackshaw S, Schell MJ, Snyder SH (1997) Neuronal nitric oxide synthase alternatively spliced forms:prominent functional localizations in the brain. Proc Natl Acad Sci USA 94:3396-401PubMedCrossRefGoogle Scholar
  44. Ellerbroek SM, Wennerberg K, Burridge K (2003) Serine phosphorylation negatively regulates RhoA in vivo. J Biol Chem 278:19023-31PubMedCrossRefGoogle Scholar
  45. Endo S, Nairn AC, Greengard P, Ito M (2003) Thr123 of rat G-substrate contributes to its action as a protein phosphatase inhibitor. Neurosci Res 45:79-89PubMedCrossRefGoogle Scholar
  46. Engert F, Bonhoeffer T (1999) Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399:66-70PubMedCrossRefGoogle Scholar
  47. Feil R, Kemp-Harper B (2006) cGMP signalling:from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications. EMBO Rep 7:149-53PubMedCrossRefGoogle Scholar
  48. Feil R, Hartmann J, Luo C, Wolfsgruber W, Schilling K, Feil S, Barski JJ, et al. (2003) Impairment of LTD and cerebellar learning by Purkinje cell-specific ablation of cGMP-dependent protein kinase I. J Cell Biol 163:295-302PubMedCrossRefGoogle Scholar
  49. Feil R, Feil S, Hofmann F (2005a) A heretical view on the role of NO and cGMP in vascular proliferative diseases. Trends Mol Med 11:71-5CrossRefGoogle Scholar
  50. Feil R, Hofmann F, Kleppisch T (2005b) Function of cGMP-dependent protein kinases in the nervous system. Rev Neurosci 16:23-41Google Scholar
  51. Feil S, Zimmermann P, Knorn A, Brummer S, Schlossmann J, Hofmann F, Feil R (2005) Distribution of cGMP-dependent protein kinase type I and its isoforms in the mouse brain and retina. Neuroscience 135:863-8PubMedCrossRefGoogle Scholar
  52. Fossier P, Tauc L, Baux G (1999) Calcium transients and neurotransmitter release at an identified synapse. Trends Neurosci 22:161-6PubMedCrossRefGoogle Scholar
  53. Francis SH, Corbin JD (1999) Cyclic nucleotide-dependent protein kinases:intracellular receptors for cAMP and cGMP action. Crit Rev Clin Lab Sci 36:275-328PubMedCrossRefGoogle Scholar
  54. Frey U, Krug M, Reymann KG, Matthies H (1988) Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res 452:57-65PubMedCrossRefGoogle Scholar
  55. Friebe A, Koesling D (2003) Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 93:96-105PubMedCrossRefGoogle Scholar
  56. Frisch C, Dere E, Silva MA, Godecke A, Schrader J, Huston JP (2000) Superior water maze performance and increase in fear-related behavior in the endothelial nitric oxide synthasedeficient mouse together with monoamine changes in cerebellum and ventral striatum. J Neurosci 20:6694-700PubMedGoogle Scholar
  57. Fukazawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38:447-60PubMedCrossRefGoogle Scholar
  58. Furchgott RF (1996) The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA 276:1186-8PubMedCrossRefGoogle Scholar
  59. Gage AT, Reyes M, Stanton PK (1997) Nitric-oxide-guanylyl-cyclase-dependent and -independent components of multiple forms of long-term synaptic depression. Hippocampus 7:286-95PubMedCrossRefGoogle Scholar
  60. Galione A (1994) Cyclic ADP-ribose, the ADP-ribosyl cyclase pathway and calcium signalling. Mol Cell Endocrinol 98:125-31PubMedCrossRefGoogle Scholar
  61. Galione A, White A, Willmott N, Turner M, Potter BV, Watson SP (1993) cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature 365:456-9PubMedCrossRefGoogle Scholar
  62. Gambaryan S, Geiger J, Schwarz UR, Butt E, Begonja A, Obergfell A, Walter U (2004) Potent in-hibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase. Blood 103:2593-600PubMedCrossRefGoogle Scholar
  63. Garthwaite J (2005) Dynamics of cellular NO-cGMP signaling. Front Biosci 10:1868-80PubMedCrossRefGoogle Scholar
  64. Garthwaite J, Boulton CL (1995) Nitric oxide signaling in the central nervous system. Annu Rev Physiol 57:683-706PubMedCrossRefGoogle Scholar
  65. Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336:385-8PubMedCrossRefGoogle Scholar
  66. Garthwaite G, Bartus K, Malcolm D, Goodwin D, Kollb-Sielecka M, Dooldeniya C, Garthwaite J (2006) Signaling from blood vessels to CNS axons through nitric oxide. J Neurosci 26:7730-40PubMedCrossRefGoogle Scholar
  67. Geiselhoringer A, Gaisa M, Hofmann F, Schlossmann J (2004) Distribution of IRAG and cGKI-isoforms in murine tissues. FEBS Lett 575:19-22PubMedCrossRefGoogle Scholar
  68. Guevara-Guzman R, Emson PC, Kendrick KM (1994) Modulation of in vivo striatal transmitter release by nitric oxide and cyclic GMP. J Neurochem 62:807-10PubMedCrossRefGoogle Scholar
  69. Haley JE, Wilcox GL, Chapman PF (1992) The role of nitric oxide in hippocampal long-term potentiation. Neuron 8:211-6PubMedCrossRefGoogle Scholar
  70. Hall KU, Collins SP, Gamm DM, Massa E, DePaoli-Roach AA, Uhler MD (1999) Phosphorylation-dependent inhibition of protein phosphatase-1 by G-substrate. A Purkinje cell substrate of the cyclic GMP-dependent protein kinase. J Biol Chem 274:3485-95PubMedCrossRefGoogle Scholar
  71. Han J, Mark MD, Li X, Xie M, Waka S, Rettig J, Herlitze S (2006) RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels. Neuron 51:575-86PubMedCrossRefGoogle Scholar
  72. Hanbauer I, Wink D, Osawa Y, Edelman GM, Gally JA (1992) Role of nitric oxide in NMDAevoked release of [3H]-dopamine from striatal slices. Neuroreport 3:409-12PubMedCrossRefGoogle Scholar
  73. Hartell NA (1994) cGMP acts within cerebellar Purkinje cells to produce long term depression via mechanisms involving PKC and PKG. Neuroreport 5:833-6PubMedCrossRefGoogle Scholar
  74. Haug LS, Jensen V, Hvalby O, Walaas SI, Ostvold AC (1999) Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic nucleotide-dependent kinases in vitro and in rat cerebellar slices in situ. J Biol Chem 274:7467-73PubMedCrossRefGoogle Scholar
  75. Haul S, Godecke A, Schrader J, Haas HL, Luhmann HJ (1999) Impairment of neocortical long-term potentiation in mice deficient of endothelial nitric oxide synthase. J Neurophysiol 81:494-7PubMedGoogle Scholar
  76. Hauser W, Knobeloch KP, Eigenthaler M, Gambaryan S, Krenn V, Geiger J, Glazova M, et al. (1999) Megakaryocyte hyperplasia and enhanced agonist-induced platelet activation in vasodilator-stimulated phosphoprotein knockout mice. Proc Natl Acad Sci USA 96:8120-5PubMedCrossRefGoogle Scholar
  77. Hawkins RD, Son H, Arancio O (1998) Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. Prog Brain Res 118:155-72PubMedCrossRefGoogle Scholar
  78. Hebb AL, Robertson HA (2006) Role of phosphodiesterases in neurological and psychiatric disease. Curr Opin Pharmacol (doi:10.1016/j.coph.2006.08.014)Google Scholar
  79. Hebb DO (1949) The organisation of behavior. A neurophsychological theory. Wiley, New YorkGoogle Scholar
  80. Herman JP, Langub MC, Jr., Watson RE, Jr. (1993) Localization of C-type natriuretic peptide mRNA in rat hypothalamus. Endocrinology 133:1903-6PubMedCrossRefGoogle Scholar
  81. Higashida H, Hashii M, Yokoyama S, Hoshi N, Chen XL, Egorova A, Noda M, et al. (2001) Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal transduction from receptors to ADP-ribosyl cyclase. Pharmacol Ther 90:283-96PubMedCrossRefGoogle Scholar
  82. Hinds HL, Goussakov I, Nakazawa K, Tonegawa S, Bolshakov VY (2003) Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse. Proc Natl Acad Sci USA 100:4275-80PubMedCrossRefGoogle Scholar
  83. Hofmann F, Sold G (1972) A protein kinase activity from rat cerebellum stimulated by guanosine3′ 5 -monophosphate. Biochem Biophys Res Commun 49:1100-7PubMedCrossRefGoogle Scholar
  84. Hofmann F, Biel M, Feil R, Kleppisch T (2003) Mouse models of NO/natriuretic peptide/cGMP kinase signaling. In:Hein L, Offermanns S (eds) Handbook of Experimental Pharmacology, pp 95-130Google Scholar
  85. Hofmann F, Biel M, Kaupp UB (2005) International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev 57:455-62PubMedCrossRefGoogle Scholar
  86. Hofmann F, Feil R, Kleppisch T, Schlossmann J (2006) Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev 86:1-23PubMedCrossRefGoogle Scholar
  87. Hollinger S, Hepler JR (2002) Cellular regulation of RGS proteins:modulators and integrators of G protein signaling. Pharmacol Rev 54:527-59PubMedCrossRefGoogle Scholar
  88. Hopper RA, Garthwaite J (2006) Tonic and phasic nitric oxide signals in hippocampal long-term potentiation. J Neurosci 26:11513-21PubMedCrossRefGoogle Scholar
  89. Huang CC, Chan SH, Hsu KS (2003) cGMP/protein kinase G-dependent potentiation of glutamatergic transmission induced by nitric oxide in immature rat rostral ventrolateral medulla neurons in vitro. Mol Pharmacol 64:521-32PubMedCrossRefGoogle Scholar
  90. Huang EP (1997) Synaptic plasticity:a role for nitric oxide in LTP. Curr Biol 7:R141-3PubMedCrossRefGoogle Scholar
  91. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265-9PubMedCrossRefGoogle Scholar
  92. Ingi T, Krumins AM, Chidiac P, Brothers GM, Chung S, Snow BE, Barnes CA, et al. (1998) Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J Neurosci 18:7178-88PubMedGoogle Scholar
  93. Ingram SL, Williams JT (1996) Modulation of the hyperpolarization-activated current (Ih) by cyclic nucleotides in guinea-pig primary afferent neurons. J Physiol 492 ( Pt 1):97-106PubMedGoogle Scholar
  94. Ito M (2001) Cerebellar long-term depression:characterization, signal transduction, and functional roles. Physiol Rev 81:1143-95PubMedGoogle Scholar
  95. Ito M (2002) Historical review of the significance of the cerebellum and the role of Purkinje cells in motor learning. Ann N Y Acad Sci 978:273-88PubMedCrossRefGoogle Scholar
  96. Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH (2001) Protein S-nitrosylation:a physiological signal for neuronal nitric oxide. Nat Cell Biol 3:193-7PubMedCrossRefGoogle Scholar
  97. Kano T, Shimizu-Sasamata M, Huang PL, Moskowitz MA, Lo EH (1998) Effects of nitric oxide synthase gene knockout on neurotransmitter release in vivo. Neuroscience 86:695-9PubMedCrossRefGoogle Scholar
  98. Kantor DB, Lanzrein M, Stary SJ, Sandoval GM, Smith WB, Sullivan BM, Davidson N, et al. (1996) A role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue. Science 274:1744-8PubMedCrossRefGoogle Scholar
  99. Kaupp UB, Niidome T, Tanabe T, Terada S, B önigk W, St ühmer W, Cook NJ, et al. (1989) Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342:762-6PubMedCrossRefGoogle Scholar
  100. Kim HY, Kim SJ, Kim J, Oh SB, Cho H, Jung SJ (2005) Effect of nitric oxide on hyperpolarizationactivated current in substantia gelatinosa neurons of rats. Biochem Biophys Res Commun 338:1648-53PubMedCrossRefGoogle Scholar
  101. Kingston PA, Zufall F, Barnstable CJ (1996) Rat hippocampal neurons express genes for both rod retinal and olfactory cyclic nucleotide-gated channels:novel targets for cAMP/cGMP function. Proc Natl Acad Sci USA 93:10440-5PubMedCrossRefGoogle Scholar
  102. Kleppisch T, Pfeifer A, Klatt P, Ruth P, Montkowski A, Fassler R, Hofmann F (1999) Long-term potentiation in the hippocampal CA1 region of mice lacking cGMP-dependent kinases is normal and susceptible to inhibition of nitric oxide synthase. J Neurosci 19:48-55PubMedGoogle Scholar
  103. Kleppisch T, Wolfsgruber W, Feil S, Allmann R, Wotjak CT, Goebbels S, Nave K-A, et al. (2003) Hippocampal cyclic GMP-dependent protein kinase I supports an age- and protein synthesisdependent component of long-term potentiation but is not essential for spatial reference and contextual memory. J Neurosci 23:6005-12PubMedGoogle Scholar
  104. Klyachko VA, Ahern GP, Jackson MB (2001) cGMP-mediated facilitation in nerve terminals by enhancement of the spike afterhyperpolarization. Neuron 31:1015-25PubMedCrossRefGoogle Scholar
  105. Koesling D, Mullershausen F, Lange A, Friebe A, Mergia E, Wagner C, Russwurm M (2005) Negative feedback in NO/cGMP signalling. Biochem Soc Trans 33:1119-22PubMedCrossRefGoogle Scholar
  106. Komatsu Y, Nakao K, Suga S, Ogawa Y, Mukoyama M, Arai H, Shirakami G, et al. (1991) C-type natriuretic peptide (CNP) in rats and humans. Endocrinology 129:1104-6PubMedCrossRefGoogle Scholar
  107. Korschen HG, Illing M, Seifert R, Sesti F, Williams A, Gotzes S, Colville C, et al. (1995) A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor. Neuron 15:627-36PubMedCrossRefGoogle Scholar
  108. Koutalos Y, Yau KW (1996) Regulation of sensitivity in vertebrate rod photoreceptors by calcium. Trends Neurosci 19:73-81PubMedCrossRefGoogle Scholar
  109. Kuhn M (2004) Molecular physiology of natriuretic peptide signalling. Basic Res Cardiol 99:76-82PubMedCrossRefGoogle Scholar
  110. Landgraf W, Hofmann F, Pelton JT, Huggins JP (1990) Effects of cyclic GMP on the secondary structure of cyclic GMP dependent protein kinase and analysis of the enzyme’s amino-terminal domain by far-ultraviolet circular dichroism. Biochemistry 29:9921-8PubMedCrossRefGoogle Scholar
  111. Larkman AU, Jack JJ (1995) Synaptic plasticity:hippocampal LTP. Curr Opin Neurobiol 5:324-34PubMedCrossRefGoogle Scholar
  112. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, et al. (2006) Genomewide atlas of gene expression in the adult mouse brain. Nature 445:168-76PubMedCrossRefGoogle Scholar
  113. Lev-Ram V, Makings LR, Keitz PF, Kao JP, Tsien RY (1995) Long-term depression in cerebellar Purkinje neurons results from coincidence of nitric oxide and depolarization-induced Ca2+ transients. Neuron 15:407-15PubMedCrossRefGoogle Scholar
  114. Lev-Ram V, Jiang T, Wood J, Lawrence DS, Tsien RY (1997a) Synergies and coincidence requirements between NO, cGMP, and Ca2+ in the induction of cerebellar long-term depression. Neuron 18:1025-38CrossRefGoogle Scholar
  115. Lev-Ram V, Nebyelul Z, Ellisman MH, Huang PL, Tsien RY (1997b) Absence of cerebellar longterm depression in mice lacking neuronal nitric oxide synthase. Learn Mem 4:169-77CrossRefGoogle Scholar
  116. Lisman J (2003) Actin’s actions in LTP-induced synapse growth. Neuron 38:361-2PubMedCrossRefGoogle Scholar
  117. Lisman J, Raghavachari S (2006) A unified model of the presynaptic and postsynaptic changes during LTP at CA1 synapses. Sci STKE 2006:re11Google Scholar
  118. Lisman J, Schulman H, Cline H (2002) The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 3:175-90PubMedCrossRefGoogle Scholar
  119. Liu S, Ninan I, Antonova I, Battaglia F, Trinchese F, Narasanna A, Kolodilov N, et al. (2004) alphaSynuclein produces a long-lasting increase in neurotransmitter release. Embo J 23:4506-16PubMedCrossRefGoogle Scholar
  120. Lohmann SM, Walter U, Miller PE, Greengard P, De Camilli P (1981) Immunohistochemical lo-calization of cyclic GMP-dependent protein kinase in mammalian brain. Proc Natl Acad Sci USA 78:653-7PubMedCrossRefGoogle Scholar
  121. Lu YF, Hawkins RD (2002) Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB phosphorylation in the hippocampus. J Neurophysiol 88:1270-8PubMedGoogle Scholar
  122. Lu YF, Kandel ER, Hawkins RD (1999) Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J Neurosci 19:10250-61PubMedGoogle Scholar
  123. Malenka RC, Bear MF (2004) LTP and LTD:an embarrassment of riches. Neuron 44:5-21PubMedCrossRefGoogle Scholar
  124. Maletic-Savatic M, Malinow R, Svoboda K (1999) Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283:1923-7PubMedCrossRefGoogle Scholar
  125. Manahan-Vaughan D, Braunewell KH (1999) Novelty acquisition is associated with induction of hippocampal long-term depression. Proc Natl Acad Sci USA 96:8739-44PubMedCrossRefGoogle Scholar
  126. Marshall SJ, Senis YA, Auger JM, Feil R, Hofmann F, Salmon G, Peterson JT, et al. (2004) GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMPdependent kinase. Blood 103:2601-9PubMedCrossRefGoogle Scholar
  127. Martin TF (2001) PI(4,5)P(2) regulation of surface membrane traffic. Curr Opin Cell Biol 13:493-9PubMedCrossRefGoogle Scholar
  128. Meffert MK, Calakos NC, Scheller RH, Schulman H (1996) Nitric oxide modulates synaptic vesicle docking fusion reactions. Neuron 16:1229-36PubMedCrossRefGoogle Scholar
  129. Menniti FS, Faraci WS, Schmidt CJ (2006) Phosphodiesterases in the CNS:targets for drug development. Nat Rev Drug Discov 5:660-70PubMedCrossRefGoogle Scholar
  130. Mergia E, Russwurm M, Zoidl G, Koesling D (2003) Major occurrence of the new alpha2beta1 isoform of NO-sensitive guanylyl cyclase in brain. Cell Signal 15:189-95PubMedCrossRefGoogle Scholar
  131. Mergia E, Haghikia A, Mittmann T, Friebe A, Koesling D (2006) Vascular and neuronal functions of the NO-sensitive guanylyl cyclase isoforms (alpha(1)-GC, alpha(2)-GC). Naunyn Schmiedebergs Arch Pharmacol 372 (Suppl. 1):45-46Google Scholar
  132. Micheva KD, Holz RW, Smith SJ (2001) Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity. J Cell Biol 154:355-68PubMedCrossRefGoogle Scholar
  133. Micheva KD, Buchanan J, Holz RW, Smith SJ (2003) Retrograde regulation of synaptic vesicle endocytosis and recycling. Nat Neurosci 6:925-32PubMedCrossRefGoogle Scholar
  134. Montague PR, Gancayco CD, Winn MJ, Marchase RB, Friedlander MJ (1994) Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science 263:973-7PubMedCrossRefGoogle Scholar
  135. Moosmang S, Biel M, Hofmann F, Ludwig A (1999) Differential distribution of four hyperpolarization-activated cation channels in mouse brain. Biol Chem 380:975-80PubMedCrossRefGoogle Scholar
  136. Muller U (1997) The nitric oxide system in insects. Prog Neurobiol 51:363-81PubMedCrossRefGoogle Scholar
  137. Ninan I, Arancio O (2004) Presynaptic CaMKII is necessary for synaptic plasticity in cultured hippocampal neurons. Neuron 42:129-41PubMedCrossRefGoogle Scholar
  138. Nishi A, Watanabe Y, Higashi H, Tanaka M, Nairn AC, Greengard P (2005) Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades. Proc Natl Acad Sci USA 102:1199-204PubMedCrossRefGoogle Scholar
  139. Notomi T, Shigemoto R (2004) Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. J Comp Neurol 471:241-76PubMedCrossRefGoogle Scholar
  140. O’Dell TJ, Hawkins RD, Kandel ER, Arancio O (1991) Tests of the roles of two diffusible substances in long-term potentiation:evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci USA 88:11285-9PubMedCrossRefGoogle Scholar
  141. O’Dell TJ, Huang PL, Dawson TM, Dinerman JL, Snyder SH, Kandel ER, Fishman MC (1994) Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS. Science 265:542-6PubMedCrossRefGoogle Scholar
  142. Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, et al. (2000) Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci USA 97:12272-7PubMedCrossRefGoogle Scholar
  143. Osborne SL, Meunier FA, Schiavo G (2001) Phosphoinositides as key regulators of synaptic function. Neuron 32:9-12PubMedCrossRefGoogle Scholar
  144. Oster H, Werner C, Magnone MC, Mayser H, Feil R, Seeliger MW, Hofmann F, et al. (2003) cGMP-dependent protein kinase II modulates mPer1 and mPer2 gene induction and influences phase shifts of the circadian clock. Curr Biol 13:725-33PubMedCrossRefGoogle Scholar
  145. Pape HC, Mager R (1992) Nitric oxide controls oscillatory activity in thalamocortical neurons. Neuron 9:441-8PubMedCrossRefGoogle Scholar
  146. Parent A, Schrader K, Munger SD, Reed RR, Linden DJ, Ronnett GV (1998) Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic nucleotide-gated channel type 1 null mouse. J Neurophysiol 79:3295-301PubMedGoogle Scholar
  147. Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC (2006) Storage of spatial information by the maintenance mechanism of LTP. Science 313:1141-4PubMedCrossRefGoogle Scholar
  148. Pedram A, Razandi M, Kehrl J, Levin ER (2000) Natriuretic peptides inhibit G protein activation. Mediation through cross-talk between cyclic GMP-dependent protein kinase and regulators of G protein-signaling proteins. J Biol Chem 275:7365-72PubMedCrossRefGoogle Scholar
  149. Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, Wang GX, et al. (1998) Defective smooth muscle regulation in cGMP kinase I-deficient mice. Embo J 17:3045-51PubMedCrossRefGoogle Scholar
  150. Pfeifer A, Ruth P, Dostmann W, Sausbier M, Klatt P, Hofmann F (1999) Structure and function of cGMP-dependent protein kinases. Rev Physiol Biochem Pharmacol 135:105-49PubMedCrossRefGoogle Scholar
  151. Pogun S, Baumann MH, Kuhar MJ (1994) Nitric oxide inhibits [3H]dopamine uptake. Brain Res 641:83-91PubMedCrossRefGoogle Scholar
  152. Pose I, Sampogna S, Chase MH, Morales FR (2003) Mesencephalic trigeminal neurons are innervated by nitric oxide synthase-containing fibers and respond to nitric oxide. Brain Res 960:81-9PubMedCrossRefGoogle Scholar
  153. Prast H, Philippu A (1992) Nitric oxide releases acetylcholine in the basal forebrain. Eur J Phar-macol 216:139-40CrossRefGoogle Scholar
  154. Prast H, Philippu A (2001) Nitric oxide as modulator of neuronal function. Prog Neurobiol 64:51-68PubMedCrossRefGoogle Scholar
  155. Qian Y, Chao DS, Santillano DR, Cornwell TL, Nairn AC, Greengard P, Lincoln TM, et al. (1996) cGMP-dependent protein kinase in dorsal root ganglion:relationship with nitric oxide synthase and nociceptive neurons. J Neurosci 16:3130-8PubMedGoogle Scholar
  156. Reid CA, Bekkers JM, Clements JD (2003) Presynaptic Ca2+ channels:a functional patchwork. Trends Neurosci 26:683-7PubMedCrossRefGoogle Scholar
  157. Reinhard M, Jarchau T, Walter U (2001) Actin-based motility:stop and go with Ena/VASP proteins. Trends Biochem Sci 26:243-9PubMedCrossRefGoogle Scholar
  158. Revermann M, Maronde E, Ruth P, Korf HW (2002) Protein kinase G I immunoreaction is colocalized with arginine-vasopressin immunoreaction in the rat suprachiasmatic nucleus. Neurosci Lett 334:119-22PubMedCrossRefGoogle Scholar
  159. Reyes M, Stanton PK (1996) Induction of hippocampal long-term depression requires release of Ca2+ from separate presynaptic and postsynaptic intracellular stores. J Neurosci 16:5951-60PubMedGoogle Scholar
  160. Reyes-Harde M, Empson R, Potter BV, Galione A, Stanton PK (1999a) Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus. Proc Natl Acad Sci USA 96:4061-6CrossRefGoogle Scholar
  161. Reyes-Harde M, Potter BV, Galione A, Stanton PK (1999b) Induction of hippocampal LTD requires nitric-oxide-stimulated PKG activity and Ca2+ release from cyclic ADP-ribosesensitive stores. J Neurophysiol 82:1569-76Google Scholar
  162. Riccio A, Alvania RS, Lonze BE, Ramanan N, Kim T, Huang Y, Dawson TM, et al. (2006) A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol Cell 21:283-94PubMedCrossRefGoogle Scholar
  163. Rieke F, Schwartz EA (1994) A cGMP-gated current can control exocytosis at cone synapses. Neuron 13:863-73PubMedCrossRefGoogle Scholar
  164. Robinson RB, Siegelbaum SA (2003) Hyperpolarization-activated cation currents:from molecules to physiological function. Annu Rev Physiol 65:453-80PubMedCrossRefGoogle Scholar
  165. Rogan MT, Staubli UV, LeDoux JE (1997) Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390:604-7PubMedCrossRefGoogle Scholar
  166. Russwurm M, Koesling D (2004) Guanylyl cyclase:NO hits its target. Biochem Soc Symp:51-63Google Scholar
  167. Ruth P, Landgraf W, Keilbach A, May B, Egleme C, Hofmann F (1991) The activation of expressed cGMP-dependent protein kinase isozymes I alpha and I beta is determined by the different amino-termini. Eur J Biochem 202:1339-44PubMedCrossRefGoogle Scholar
  168. Ryan TA, Reuter H, Wendland B, Schweizer FE, Tsien RW, Smith SJ (1993) The kinetics of synaptic vesicle recycling measured at single presynaptic boutons. Neuron 11:713-24PubMedCrossRefGoogle Scholar
  169. Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, Beavo JA (2002) Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem 277:3310-7PubMedCrossRefGoogle Scholar
  170. Sausbier M, Schubert R, Voigt V, Hirneiss C, Pfeifer A, Korth M, Kleppisch T, et al. (2000) Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87:825-30PubMedGoogle Scholar
  171. Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J, Chardin P, et al. (2000) Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275:21722-9PubMedCrossRefGoogle Scholar
  172. Savchenko A, Barnes S, Kramer RH (1997) Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide. Nature 390:694-8PubMedGoogle Scholar
  173. Schmidt H, Werner M, Heppenstall PA, Henning M, Mor é MI, K ühbandner S, Lewin GR, et al. (2002) cGMP-mediated signalling via cGKIalpha is required for the guidance and connectivity of sensory axons. J Cell Biol 159:489-98PubMedCrossRefGoogle Scholar
  174. Schuman EM, Madison DV (1991) A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254:1503-6PubMedCrossRefGoogle Scholar
  175. Schuman EM, Meffert MK, Schulman H, Madison DV (1994) An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation. Proc Natl Acad Sci USA 91:11958-62PubMedCrossRefGoogle Scholar
  176. Shimizu-Albergine M, Rybalkin SD, Rybalkina IG, Feil R, Wolfsgruber W, Hofmann F, Beavo JA (2003) Individual cerebellar Purkinje cells express different cGMP phosphodiesterases (PDEs):in vivo phosphorylation of cGMP-specific PDE (PDE5) as an indicator of cGMP-dependent protein kinase (PKG) activation. J Neurosci 23:6452-9PubMedGoogle Scholar
  177. Shin JH, Linden DJ (2005) An NMDA receptor/nitric oxide cascade is involved in cerebellar LTD but is not localized to the parallel fiber terminal. J Neurophysiol 94:4281-9PubMedCrossRefGoogle Scholar
  178. Son H, Hawkins RD, Martin K, Kiebler M, Huang PL, Fishman MC, Kandel ER (1996) Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell 87:1015-23PubMedCrossRefGoogle Scholar
  179. Sonnenburg WK, Beavo JA (1994) Cyclic GMP and regulation of cyclic nucleotide hydrolysis. Adv Pharmacol 26:87-114PubMedCrossRefGoogle Scholar
  180. Sorkin LS (1993) NMDA evokes an L-NAME sensitive spinal release of glutamate and citrulline. Neuroreport 4:479-82PubMedCrossRefGoogle Scholar
  181. Sporns O, Jenkinson S (1997) Potassium ion- and nitric oxide-induced exocytosis from populations of hippocampal synapses during synaptic maturation in vitro. Neuroscience 80:1057-73PubMedCrossRefGoogle Scholar
  182. Stamler JS, Toone EJ, Lipton SA, Sucher NJ (1997) (S)NO signals:translocation, regulation, and a consensus motif. Neuron 18:691-6PubMedCrossRefGoogle Scholar
  183. Stanarius A, Topel I, Schulz S, Noack H, Wolf G (1997) Immunocytochemistry of endothelial nitric oxide synthase in the rat brain:a light and electron microscopical study using the tyramide signal amplification technique. Acta Histochem 99:411-29PubMedGoogle Scholar
  184. Stanton PK, Heinemann U, Muller W (2001) FM1-43 imaging reveals cGMP-dependent long-term depression of presynaptic transmitter release. J Neurosci RC21:167Google Scholar
  185. Stanton PK, Winterer J, Bailey CP, Kyrozis A, Raginov I, Laube G, Veh RW, et al. (2003) Longterm depression of presynaptic release from the readily releasable vesicle pool induced by NMDA receptor-dependent retrograde nitric oxide. J Neurosci 23:5936-44PubMedGoogle Scholar
  186. Stanton PK, Winterer J, Zhang XL, Muller W (2005) Imaging LTP of presynaptic release of FM1-43 from the rapidly recycling vesicle pool of Schaffer collateral-CA1 synapses in rat hippocampal slices. Eur J Neurosci 22:2451-61PubMedCrossRefGoogle Scholar
  187. Starke K (1981) Presynaptic receptors. Annu Rev Pharmacol Toxicol 21:7-30PubMedCrossRefGoogle Scholar
  188. Stewart TL, Michel AD, Black MD, Humphrey PP (1996) Evidence that nitric oxide causes calcium-independent release of [3H] dopamine from rat striatum in vitro. J Neurochem 66:131-7PubMedCrossRefGoogle Scholar
  189. Sudoh T, Minamino N, Kangawa K, Matsuo H (1988) Brain natriuretic peptide-32:N-terminal six amino acid extended form of brain natriuretic peptide identified in porcine brain. Biochem Biophys Res Commun 155:726-32PubMedCrossRefGoogle Scholar
  190. Sudoh T, Minamino N, Kangawa K, Matsuo H (1990) C-type natriuretic peptide (CNP):a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun 168:863-70PubMedCrossRefGoogle Scholar
  191. Sullivan BM, Wong S, Schuman EM (1997) Modification of hippocampal synaptic proteins by nitric oxide-stimulated ADP ribosylation. Learn Mem 3:414-24PubMedCrossRefGoogle Scholar
  192. Sun X, Kaltenbronn KM, Steinberg TH, Blumer KJ (2005) RGS2 is a mediator of nitric oxide action on blood pressure and vasoconstrictor signaling. Mol Pharmacol 67:631-9PubMedCrossRefGoogle Scholar
  193. Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, et al. (2003) Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9:1506-12PubMedCrossRefGoogle Scholar
  194. Tegeder I, Del Turco D, Schmidtko A, Sausbier M, Feil R, Hofmann F, Deller T, et al. (2004) Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I. Proc Natl Acad Sci USA 101:3253-7PubMedCrossRefGoogle Scholar
  195. Tian M, Yang XL (2006) C-type natriuretic peptide modulates glutamate receptors on cultured rat retinal amacrine cells. Neuroscience 139:1211-20PubMedCrossRefGoogle Scholar
  196. Tsou K, Snyder GL, Greengard P (1993) Nitric oxide/cGMP pathway stimulates phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, in the substantia nigra. Proc Natl Acad Sci USA 90:3462-5PubMedCrossRefGoogle Scholar
  197. Valtschanoff JG, Weinberg RJ (2001) Laminar organization of the NMDA receptor complex within the postsynaptic density. J Neurosci 21:1211-7PubMedGoogle Scholar
  198. Wagner LE, 2nd, Li WH, Yule DI (2003) Phosphorylation of type-1 inositol 1,4,5-trisphosphate receptors by cyclic nucleotide-dependent protein kinases:a mutational analysis of the functionally important sites in the S2+ and S2− splice variants. J Biol Chem 278:45811-7PubMedCrossRefGoogle Scholar
  199. Wall ME, Francis SH, Corbin JD, Grimes K, Richie-Jannetta R, Kotera J, Macdonald BA, et al. (2003) Mechanisms associated with cGMP binding and activation of cGMP-dependent protein kinase. Proc Natl Acad Sci USA 100:2380-5PubMedCrossRefGoogle Scholar
  200. Wang HG, Lu FM, Jin I, Udo H, Kandel ER, de Vente J, Walter U, et al. (2005) Presynaptic and postsynaptic roles of NO, cGK, and RhoA in long-lasting potentiation and aggregation of synaptic proteins. Neuron 45:389-403PubMedCrossRefGoogle Scholar
  201. Wang X, Robinson PJ (1997) Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J Neurochem 68:443-56PubMedCrossRefGoogle Scholar
  202. Wang YT, Linden DJ (2000) Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25:635-47PubMedCrossRefGoogle Scholar
  203. Welsh JP, Yamaguchi H, Zeng XH, Kojo M, Nakada Y, Takagi A, Sugimori M, et al. (2005) Normal motor learning during pharmacological prevention of Purkinje cell long-term depression. Proc Natl Acad Sci USA 102:17166-71PubMedCrossRefGoogle Scholar
  204. Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093-7PubMedCrossRefGoogle Scholar
  205. Wilson RI, Godecke A, Brown RE, Schrader J, Haas HL (1999) Mice deficient in endothelial nitric oxide synthase exhibit a selective deficit in hippocampal long-term potentiation. Neuroscience 90:1157-65PubMedCrossRefGoogle Scholar
  206. Xia C, Bao Z, Yue C, Sanborn BM, Liu M (2001) Phosphorylation and regulation of Gprotein-activated phospholipase C-beta 3 by cGMP-dependent protein kinases. J Biol Chem 276:19770-7PubMedCrossRefGoogle Scholar
  207. Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234-7PubMedCrossRefGoogle Scholar
  208. Xue J, Wang X, Malladi CS, Kinoshita M, Milburn PJ, Lengyel I, Rostas JA, et al. (2000) Phosphorylation of a new brain-specific septin, G-septin, by cGMP-dependent protein kinase. J Biol Chem 275:10047-56PubMedCrossRefGoogle Scholar
  209. Xue J, Milburn PJ, Hanna BT, Graham ME, Rostas JA, Robinson PJ (2004) Phosphorylation of septin 3 on Ser-91 by cGMP-dependent protein kinase-I in nerve terminals. Biochem J 381:753-60PubMedCrossRefGoogle Scholar
  210. Yu X, Duan KL, Shang CF, Yu HG, Zhou Z (2004) Calcium influx through hyperpolarizationactivated cation channels (I(h) channels) contributes to activity-evoked neuronal secretion. Proc Natl Acad Sci USA 101:1051-6PubMedCrossRefGoogle Scholar
  211. Yu YC, Cao LH, Yang XL (2006) Modulation by brain natriuretic peptide of GABA receptors on rat retinal ON-type bipolar cells. J Neurosci 26:696-707PubMedCrossRefGoogle Scholar
  212. Zhang J, Dawson VL, Dawson TM, Snyder SH (1994) Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263:687-9PubMedCrossRefGoogle Scholar
  213. Zhuang S, Nguyen GT, Chen Y, Gudi T, Eigenthaler M, Jarchau T, Walter U, et al. (2004) Vasodilator-stimulated phosphoprotein activation of serum-response element-dependent transcription occurs downstream of RhoA and is inhibited by cGMP-dependent protein kinase phosphorylation. J Biol Chem 279:10397-407PubMedCrossRefGoogle Scholar
  214. Zhuo M, Hu Y, Schultz C, Kandel ER, Hawkins RD (1994) Role of guanylyl cyclase and cGMPdependent protein kinase in long-term potentiation. Nature 368:635-9PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Robert Feil
    • 1
  • Thomas Kleppisch
    • 2
  1. 1.Interfakultäres Institut für BiochemieUniversität TübingenMünchenGermany
  2. 2.Institut für Pharmakologie und ToxikologieTechnische Universität MüunchenMünchenGermany

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