Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells

Hartell, Nick A.; Furuya, Shigeki; Jacoby, Sonja; Okada, Daisuke

doi:10.1097/00001756-200101220-00013

Cited by 39 publications

(30 citation statements)

References 22 publications

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“…Cerebellar nerve terminals could be a physiological source for cGMP affecting the kainate autoreceptor response; however, we cannot exclude that glial or Purkinje cells, where cGMP accumulates after glutamate receptor/nitric oxide/guanylyl cyclase pathway activation or parallel fiber stimulation (Tsuyama et al, 1999;Hartell et al, 2001;Honda et al, 2001;Marcoli et al, 2006b) and from which cGMP may be released (Luo et al, 1994), might contribute as a source for extracellular cGMP.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Cervetto¹,

Maura²,

Marcoli³

2009

J Pharmacol Exp Ther

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We found that both ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate autoreceptors were present on the glutamate-releasing terminals of cerebellar parallel/climbing fibers and that they functioned as facilitatory autoreceptors. Extracellular cGMP inhibited the neurotransmitter release evoked by presynaptic kainate receptor activation; the inhibitory effect of extracellular cGMP was selective for the kainate autoreceptor-mediated response and did not affect the AMPA autoreceptor-mediated response. Endogenously synthesized cGMP might be the physiological source for the extracellular cGMP modulating the response to kainate autoreceptor activation.It has long been known that intracellular cGMP, whose production is linked through nitric oxide formation to the activation of cerebellar glutamatergic transmission, functions as a crucial cerebellar intracellular messenger, e.g., in the long-term depression of excitatory transmission at parallel fiber-Purkinje cell synapses (Ito and Karachot, 1992;Boxall and Garthwaite, 1996;Daniel et al., 1998;Hartell, 2001, and references therein). It is also known that cGMP can be actively transported from the intracellular compartment to extracellular fluid through membrane transport proteins (including a probenecid-sensitive transporter and members of the multidrug-resistance protein family; Sager, 2004). Activation of glutamate receptors has been shown to increase intracellular cGMP levels and to cause cGMP release from the intracellular to the extracellular compartment in cultured cerebellar neurons (Montoliu et al., 1999) or in cerebellar slices (in a probenecid-sensitive way) (Tjörnhammar et al., 1986), with the extracellular cGMP levels matching the intracellular levels. Indeed, extracellular cGMP has been exploited in in vivo models as a reliable measure of activation of cerebellar glutamatergic transmission (Wood and Rao, 1991;Luo et al., 1994;Fedele and Raiteri, 1999). Nevertheless, the roles of extracellular cGMP in the cerebellum have hardly been studied. Interference of cGMP with the response to activation of ionotropic glutamate receptors has been occasionally reported in cultured cerebellar cells; extracellular cGMP has been reported to inhibit glutamate responses at ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate receptors in Purkinje cells and in granules (Linden et al., 1995;Poulopoulou and Nowak, 1998) and to prevent glutamate neurotoxicity in cerebellar neurons (Montoliu et al., 1999). It has also been reported to inhibit binding to a kainate low-affinity site in rat cerebellum membranes (Migani et al., 1997).We investigated the ability of extracellular cGMP to interfere with AMPA/kainate receptor responses in the adult cerebellum, by using superfused purified synaptosomes, which allow direct functional evidence of presynaptic release-regulating receptors. Two aspects were investigated: 1) the presence and functioning of AMPA and kainate autoreceptors on the glutamatergic terminals of rat cerebellar parallel/climbin...

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Section: Discussionmentioning

confidence: 99%

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Cervetto¹,

Maura²,

Marcoli³

2009

J Pharmacol Exp Ther

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“…In addition, the cerebellum has the highest levels of cGMP in the mouse brain (Greenberg et al, 1978) and the distribution of cGMPand nNOS-immunoreactivity was similar in the rat brain (De Vente et al, 1998). Several studies have detailed the role of NO in cerebellar LTD through a probable action of NO produced by granular cells on Purkinje neurons (Hartell et al, 2001;Shibuki and Okada, 1991). Opposite to what observed in rodents, nNOS-ir Purkinje cells have been observed in the human cerebellum (Egberongbe et al, 1994).…”

Section: Cerebellummentioning

confidence: 93%

Distribution of nitric oxide synthase immunoreactivity in the mouse brain

Gotti

Sica

Panzica

2005

Microsc. Res. Tech.

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Nitric oxide (NO) is a gaseous intercellular messenger with a wide range of neural functions. NO is synthesized by activation of different isoforms of nitric oxide synthases (NOS). At present NOS immunoreactivity has been described in mouse brain in restricted and definite areas and no detailed mapping studies have yet been reported for NOS immunoreactivity. We have studied the distribution of neuronal NOS-containing neurons in the brain of three months male mice, using a specific commercial polyclonal antibody against the neuronal isoform of nitric oxide synthase (nNOS). Neuronal cell bodies exhibiting nNOS immunoreactivity were found in several distinct nuclei throughout the brain. The neurons that were positively stained exhibited different intensities of reaction. In some brain areas (i.e., cortex, striatum, tegmental nuclei) neurons were intensely stained in a Golgi-like fashion. In other regions, immunoreactive cells are moderately stained (i.e., magnocellular nucleus of the posterior commissure, amygdaloid nucleus, interpeduncular nucleus, lateral periaqueductal gray) or weakly stained (i.e., vascular organ of the lamina terminalis, hippocampus, inferior colliculus, reticular nucleus). In the mouse, the NO-producing system appears well developed and widely diffused. In particular, nNOS immunoreactive neurons seem chiefly present in several sensory pathways like all the nuclei of the olfactory system, as well as in many regions of the lymbic system. These data suggest a widespread role for the NO system in the mouse nervous system.

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“…CF input stimulates the MAP kinase cascade, whereas PF input activates the nitric oxide (NO)/cGMP pathway, which plays a gating role in allowing activation of the MAP kinase cascade. However, because activation of the NO/cGMP pathway is too slow (order of minutes) to detect subsecond timing (Hartell et al, 2001), IP 3 Rs and the upstream pathways must detect the timing of the PF and CF inputs. Wang et al (2000) have proposed that IP 3 Rs themselves may detect the temporal order of the changes in IP 3 and Ca 2ϩ .…”

Section: Ip 3 Regulation Of Camentioning

confidence: 99%

Inositol 1,4,5-Trisphosphate-Dependent Ca²⁺Threshold Dynamics Detect Spike Timing in Cerebellar Purkinje Cells

Doi

Kuroda²,

Michikawa³

et al. 2005

J. Neurosci.

112

160

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Large Ca2+signals essential for cerebellar long-term depression (LTD) at parallel fiber (PF)-Purkinje cell synapses are known to be induced when PF activation precedes climbing fiber (CF) activation by 50-200 ms, consistent with cerebellar learning theories. However, large Ca2+signals and/or LTD can also be induced by massive PF stimulation alone or by photolysis of caged Ca2+or inositol 1,4,5-trisphosphate (IP3). To understand the spike-timing detection mechanisms in cerebellar LTD, we developed a kinetic model of Ca2+dynamics within a Purkinje dendritic spine. In our kinetic simulation, IP3was first produced via the metabotropic pathway of PF inputs, and the Ca2+influx in response to the CF input triggered regenerative Ca2+-induced Ca2+release from the internal stores via the IP3receptors activated by the increased IP3. The delay in IP3increase caused by the PF metabotropic pathway generated the optimal PF-CF interval. The Ca2+dynamics revealed a threshold for large Ca2+release that decreased as IP3increased, and it coherently explained the different forms of LTD. At 2.5 μmIP3, CF activation after PF activation was essential to reach the threshold for the regenerative Ca2+release. At 10 μmIP3, the same as achieved experimentally by strong IP3photolysis, the threshold was lower, and thus large Ca2+release was generated even without CF stimulation. In contrast, the basal 0.1 μmIP3level resulted in an extremely high Ca2+threshold for regenerative Ca2+release. Thus, the results demonstrated that Ca2+dynamics can detect spike timing under physiological conditions, which supports cerebellar learning theories.

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Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells

Cited by 39 publications

References 22 publications

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Distribution of nitric oxide synthase immunoreactivity in the mouse brain

Inositol 1,4,5-Trisphosphate-Dependent Ca²⁺Threshold Dynamics Detect Spike Timing in Cerebellar Purkinje Cells

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Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells

Cited by 39 publications

References 22 publications

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Distribution of nitric oxide synthase immunoreactivity in the mouse brain

Inositol 1,4,5-Trisphosphate-Dependent Ca2+Threshold Dynamics Detect Spike Timing in Cerebellar Purkinje Cells

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Inositol 1,4,5-Trisphosphate-Dependent Ca²⁺Threshold Dynamics Detect Spike Timing in Cerebellar Purkinje Cells