Direct Activation of the Olfactory Cyclic Nucleotide–Gated Channel through Modification of Sulfhydryl Groups by NO Compounds

Broillet, Marie-Christine; Firestein, Stuart

doi:10.1016/s0896-6273(00)80055-0

Neuron

1996

DOI: 10.1016/s0896-6273(00)80055-0

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Direct Activation of the Olfactory Cyclic Nucleotide–Gated Channel through Modification of Sulfhydryl Groups by NO Compounds

Marie-Christine Broillet

Stuart Firestein

Abstract: The activation of a cyclic nucleotide-gated channel is the final step in sensory transduction in olfaction. Normally, this channel is opened by the intracellular cyclic nucleotide second messenger cAMP or cGMP. However, in single channel recordings we found that donors of nitric oxide, a putative intercellular messenger, could directly activate the native olfactory neuron channel. Its action was independent of the presence of the normal ligand and did not involve the cyclic nucleotide binding site, suggesting … Show more

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Cited by 146 publications

(109 citation statements)

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“…Schmachtenberg et al (2000Schmachtenberg et al ( , 2003 reported that NO-stimulus induces outward potassium currents in 30 out of 72 olfactory cells and inward potassium currents in 3 out of 54 cells by physiological study [36,37]. In the cilia of rat olfactory cells, moreover, NO-stimulus is reported to activate or inhibit olfactory cyclic nucleotidegated (CNG) channels [5,6,28,36,37]. These reports suggest that NO is produced by the olfactory cells in response to odorant-stimulus, and has inhibitory and/or weakly excitatory effects to the olfactory cells by gating of CNG channel.…”

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confidence: 99%

Localization of eNOS in the Olfactory Epithelium of the Rat

Endo

Yamamoto

Yamaguchi-Yamada

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. Nitric oxide (NO) is a free radical and produced from L-arginine by nitric oxide synthase (NOS). Since NO is recently suggested to be involved in olfactory perception, the expression of eNOS, an isoform of NOS, was examined in the rat olfactory epithelium. The activity of NADPH-diaphorase was also examined as a marker of NOS. In the dorsomedial region of the nasal cavity, intensely positive reactions for NADPH-diaphorase were observed in the entire cytoplasm of sensory cells (olfactory cells). By immunohistochemistry, intensely positive reactions for eNOS were also found in the dorsomedial region of the nasal cavity. These reactions were observed on the free border of the olfactory epithelium. By immunoelectron microscopy, positive reactions for eNOS were found in the cilia of olfactory cells. In addition, in situ hybridization analysis of the olfactory epithelium revealed the expression of eNOS mRNA in the olfactory cells. These results indicate the presence of eNOS in the olfactory cells of the rat, and differential expression of eNOS in the olfactory epithelium depending on the regions of the nasal cavity. In addition, NO produced by eNOS may be involved in olfactory perception in the cilia of olfactory cells.KEY WORDS: eNOS, NADPH-diaphorase, nitric oxide, olfactory epithelium, rat.J. Vet. Med. Sci. 73(4): 423-430, 2011 Nitric oxide (NO) is a free radical with many functions in the cardiovascular, nervous, and immune systems [2]. Biologically, NO is produced from L-arginine by nitric oxide synthase (NOS). NOS is divided into 3 types of major isoforms, i.e., neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). The nNOS and eNOS are constitutive forms of NOS and mainly expressed in the neuronal and endothelial cells, respectively. The iNOS is an inducible form of NOS and mainly expressed in macrophages [15].Primary function of NO is the activation of soluble guanylyl cyclase (sGC) to increase cGMP levels [1]. In the cilia of the rat sensory cells (olfactory cells), it is reported that odorant-stimulus induces the increase of cGMP levels and that specific NOS inhibitor L-N G -nitro arginine or NO scavenger hemoglobin inhibits this increase [4]. These findings indicate that odorant-stimulus induces NO production in the rat olfactory cells. Schmachtenberg et al. (2000Schmachtenberg et al. ( , 2003 reported that NO-stimulus induces outward potassium currents in 30 out of 72 olfactory cells and inward potassium currents in 3 out of 54 cells by physiological study [36,37]. In the cilia of rat olfactory cells, moreover, NO-stimulus is reported to activate or inhibit olfactory cyclic nucleotidegated (CNG) channels [5,6,28,36,37]. These reports suggest that NO is produced by the olfactory cells in response to odorant-stimulus, and has inhibitory and/or weakly excitatory effects to the olfactory cells by gating of CNG channel. However, it is still unclear which type of NOS isoforms generates NO in the olfactory cells of the rat. Because it has been reported that iNOS and eNOS are expressed...

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mentioning

confidence: 99%

Localization of eNOS in the Olfactory Epithelium of the Rat

Endo

Yamamoto

Yamaguchi-Yamada

et al. 2011

The Journal of Veterinary Medical Science

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“…This may reflect a feedback mechanism, because calcium entry through NMDA receptors stimulates NO formation. The cyclic nucleotide-gated H AC channel might be normally activated by NO Snitrosylation, because HAC channels resemble olfactory cyclic nucleotide-gated channels, which are known to be activated by NO (24).…”

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confidence: 99%

Neural roles for heme oxygenase: Contrasts to nitric oxide synthase

Barañano

Snyder

2001

Proc. Natl. Acad. Sci. U.S.A.

277

204

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The heme oxygenase (HO) and nitric oxide (NO) synthase (NOS) systems display notable similarities as well as differences. HO and NOS are both oxidative enzymes using NADPH as an electron donor. The constitutive forms of the enzyme are differentially activated, with calcium entry stimulating NOS by binding to calmodulin, whereas calcium entry activates protein kinase C to phosphorylate and activate HO2. Although both NO and carbon monoxide (CO) stimulate soluble guanylyl cyclase to form cGMP, NO also S-nitrosylates selected protein targets. Both involve constitutive and inducible biosynthetic enzymes. However, functions of the inducible forms are virtual opposites. Macrophage-inducible NOS generates NO to kill other cells, whereas HO1 generates bilirubin to exert antioxidant cytoprotective effects and also provides cytoprotection by facilitating iron extrusion from cells. The neuronal form of HO, HO2, is also cytoprotective. Normally, neural NO in the brain seems to exert some sort of behavioral inhibition. However, excess release of NO in response to glutamate's Nmethyl-D-aspartate receptor activation leads to stroke damage. On the other hand, massive neuronal firing during a stroke presumably activates HO2, leading to neuroprotective actions of bilirubin. Loss of this neuroprotection after HO inhibition by mutant forms of amyloid precursor protein may mediate neurotoxicity in Familial Alzheimer's Disease. NO and CO both appear to be neurotransmitters in the brain and peripheral autonomic nervous system. They also are physiologic endothelial-derived relaxing factors for blood vessels. In the gastrointestinal pathway, NO and CO appear to function as coneurotransmitters, both stimulating soluble guanylyl cyclase to cause smooth muscle relaxation.

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“…As well as indirectly activating CNG channels by stimulating cGMP synthesis, NO directly activates CNG channels in olfactory neurons by covalently modifying the channel protein 18 . In our experiments, SNC applied directly onto excised inside-out patches from cone terminals failed to activate CNG channels and had no effect on the sensitivity of the channels to cGMP (n = 5).…”

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confidence: 99%

Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide

Savchenko

Barnes

Krämer

1997

Nature

185

146

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Cyclic-nucleotide-gated (CNG) channels in outer segments of vertebrate photoreceptors generate electrical signals in response to changes in cyclic GMP concentration during phototransduction 1 . CNG channels also allow the influx of Ca 2+ , which is essential for photoreceptor adaptation 2 . In cone photoreceptors, cGMP triggers an increase in membrane capacitance indicative of exocytosis, suggesting that CNG channels are also involved in synaptic function 3 . Here we examine whether CNG channels reside in cone terminals and whether they regulate neurotransmitter release, specifically in response to nitric oxide (NO), a retrograde transmitter that increases cGMP synthesis and potentiates synaptic transmission in the brain [4][5][6] . Using intact retina, we show that endogenous NO modulates synapses between cones and horizontal cells. In experiments on isolated cones, we show directly that CNG channels occur in clusters and are indirectly activated by S-nitrosocysteine (SNC), an NO donor. Furthermore, both SNC and pCPTcGMP, a membrane-permeant analogue of cGMP, trigger the release of transmitter from the cone terminals. The NO-induced transmitter release is suppressed by guanylate cyclase inhibitors and prevented by direct activation of CNG channels, indicating that their activation is required for NO to elicit release. These results expand our view of CNG channel function to include the regulation of synaptic transmission and mediation of the presynaptic effects of NO.Patch-clamp experiments were performed on acutely dissociated cones from lizard retina, used because they possess large (5-10 μm diameter) presynaptic terminals (labelled T in Fig. 1a). By varying the duration of proteolytic enzyme treatment and trituration, we observed either intact cones or cones devoid of outer segments and/or presynaptic terminals. To investigate whether CNG channels are present in the terminals we applied the whole-cell patch-clamp configuration to cones containing terminals and cones lacking terminals. All the cones selected for use in these experiments were devoid of outer segments, to eliminate their contribution to the whole-cell CNG current. To ensure that the cone terminals were intact and functional, we applied depolarizing voltage pulses to assay for the presence of a voltage-gated Ca 2+ current, which has been previously characterized in cones with healthy terminals 3,7,8 .The results of these experiments are shown in Fig. 1b. All cones exhibiting a voltage-gated Ca 2+ current also exhibited an inward current when the membrane-permeant cGMP analogue pCPT-cGMP (8-para-chlorothio-cGMP) was applied (9 of 9 cells). In contrast, none of the cones without terminals exhibited either the voltage-gated Ca 2+ current or pCPT-cGMP-activated current (0 of 8 cells). To confirm that the pCPT-cGMP-activated current is specifically localized to the terminal, 'whole-terminal' recordings were obtained after isolating the terminal from the inner segment by transecting the axon with a glass probe. Isolated terminals exhibited bot...

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Direct Activation of the Olfactory Cyclic Nucleotide–Gated Channel through Modification of Sulfhydryl Groups by NO Compounds

Cited by 146 publications

References 44 publications

Localization of eNOS in the Olfactory Epithelium of the Rat

Localization of eNOS in the Olfactory Epithelium of the Rat

Neural roles for heme oxygenase: Contrasts to nitric oxide synthase

Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide

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