Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain

Gibb, Barry; Garthwaite, John

doi:10.1046/j.1460-9568.2001.01421.x

Cited by 74 publications

(75 citation statements)

References 29 publications

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“…The two functionally relevant subunit compositions in the hippocampus are ␣ 1 ␤ 1 and ␣ 2 ␤ 1 . The distribution of NOsGC ␤ 1 subunit and its mRNA has been reported previously (Gibb and Garthwaite, 2001;Burette et al, 2002;Ding et al, 2004;Pifarre et al, 2007), and it was shown to be localized in pyramidal cells and in some interneurons. In addition, ␣ and ␤ subunits were found to colocalize in the same cells (Ding et al, 2004), but the ␣ 1 -and ␣ 2 -containing complexes were not distinguished.…”

Section: Introductionsupporting

confidence: 57%

“…Cell type-specific expression of NOsGC subunits and its association with nNOS Expression of the NOsGC subunit mRNA has been reported previously in 8-d-old rat hippocampus at low magnification, showing a weak ␣ 1 and a stronger ␣ 2 and ␤ 1 subunit expression (Gibb and Garthwaite, 2001). In adult rats, a large difference appears to be maintained between the ␣ 1 and ␣ 2 subunit expression at low magnification (Pifarre et al, 2007, their Fig.…”

Section: Synapse-specific No Production In Gabaergic Synapsesmentioning

confidence: 61%

“…The subunits initially termed ␣ 3 and ␤ 3 represent the human orthologs of the ␣ 1 and ␤ 1 subunits, respectively (Zabel et al, 1998). Studies have also demonstrated that, whereas ␣ 1 , ␣ 2 , and ␤ 1 subunits are abundant, there is only a negligible amount of ␤ 2 isoform in the brain (Burgunder and Cheung, 1994;Gibb and Garthwaite, 2001;Ding et al, 2004), and, even if it is expressed with ␣ 1 or ␣ 2 subunits, the complex is either not active (Koesling, 1999) or has very low activity (Gibb et al, 2003). In fact, knocking out ␤ 1 subunit results in a lethal phenotype (Friebe et al, 2007), whereas knocking out only ␣ 1 or ␣ 2 subunits does not result in lethal phenotype (Mergia et al, 2006).…”

Section: Nnos Is Associated With the Postsynaptic Density Of Gabaergimentioning

confidence: 99%

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Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Szabadits¹,

Cserép²,

Ludányi³

et al. 2007

J. Neurosci.

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Nitric oxide (NO) plays an important role in synaptic plasticity as a retrograde messenger at glutamatergic synapses. Here we describe that, in hippocampal pyramidal cells, neuronal nitric oxide synthase (nNOS) is also associated with the postsynaptic active zones of GABAergic symmetrical synapses terminating on their somata, dendrites, and axon initial segments in both mice and rats. The NO receptor nitric oxide-sensitive guanylyl cyclase (NOsGC) is present in the brain in two functional subunit compositions: ␣ 1 ␤ 1 and ␣ 2 ␤ 1 . The ␤ 1 subunit is expressed in both pyramidal cells and interneurons in the hippocampus. Using immunohistochemistry and in situ hybridization methods, we describe that the ␣ 1 subunit is detectable only in interneurons, which are always positive for ␤ 1 subunit as well; however, pyramidal cells are labeled only for ␤ 1 and ␣ 2 subunits. With double-immunofluorescent staining, we also found that most cholecystokinin-and parvalbumin-positive and smaller proportion of the somatostatin-and nNOS-positive interneurons are ␣ 1 subunit positive. We also found that the ␣ 1 subunit is present in parvalbumin-and cholecystokinin-positive interneuron terminals that establish synapses on somata, dendrites, or axon initial segments. Our results demonstrate that NOsGC, composed of ␣ 1 ␤ 1 subunits, is selectively expressed in different types of interneurons and is present in their presynaptic GABAergic terminals, in which it may serve as a receptor for NO produced postsynaptically by nNOS in the very same synapse.

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Section: Introductionsupporting

confidence: 57%

Section: Synapse-specific No Production In Gabaergic Synapsesmentioning

confidence: 61%

Section: Nnos Is Associated With the Postsynaptic Density Of Gabaergimentioning

confidence: 99%

See 1 more Smart Citation

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Szabadits¹,

Cserép²,

Ludányi³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Weak β1 expression has been described in the embryo, which increases after birth to be widely expressed in the adult (Giuili et al, 1994). The level of α2 mRNA expression in adult animals appears to be less than in 8-day-old animals, labelling being concentrated in the granule cell layer (Gibb and Garthwaite, 2001).…”

Section: Discussionmentioning

confidence: 97%

Differential expression of NO-sensitive guanylyl cyclase subunits during the development of rat cerebellar granule cells: regulation viaN-methyl-D-aspartate receptors

Jurado

Sánchez‐Prieto

Torres

2003

Journal of Cell Science

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In primary cultures of rat cerebellar granule cells with a functional network of glutamatergic neurons, the expression pattern of the different subunits of nitric-oxide (NO)-sensitive guanylyl cyclase changes during cell differentiation. These cells express the α1,α 2 and β1 subunits of NO-sensitive guanylyl cyclase and synthesize cyclic guanosine monophosphate (cGMP) in response to exogenous or endogenous nitric oxide. In this study, we determined the protein content of the α1 and β1 subunits and quantified α1, α2 and β1mRNA by reverse transcription coupled to a polymerase chain reaction (RT-PCR). Expression of the β1 subunit increased with the degree of cell differentiation, although most marked changes occurred at the α subunit level. In cells freshly isolated from rat pups on postnatal day 7 (P7) the most abundant α subunit was α1, whileα 2 appeared as the predominant subunit of this type in cultured cells. N-methyl-D-aspartate (NMDA) receptor stimulation in 7- or 14-day-cultured cells led to the upregulation of guanylyl cyclase subunit mRNAs; α2 mRNA levels undergoing most significant change. This enhanced subunit expression was accompanied by an increase in the amount of cGMP synthesized in response to NO. Thus, it seems thatα 2 subunits are increasingly expressed as granule cells mature. The presence of this subunit in the guanylyl cyclase heterodimer facilitates its localization at synaptic membranes, where the enzyme acts as a sensor for NO formed by the postsynaptic protein 95 (PSD-95)-associated neuronal NO synthase.

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“…The enzyme soluble guanylyl cyclase (sGC) has often been referred to as the "NO receptor", because of its central role in binding NO and relaying the NO signal [6]. The soluble isoforms of sGC are activated by NO, which is the product of the enzyme action of NO synthase (NOS) on L-arginine, leading to the formation and elevation of intracellular levels of the second messenger molecule, cGMP.…”

Section: No Signaling In the Cnsmentioning

confidence: 99%

Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Thatcher

Bennett²,

Reynolds³

2005

CAR

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Nitric oxide is multifunctional messenger molecule in the brain, playing important roles including in learning and memory and in regulating the expression of trophic factors that may be reduced with aging. Small molecules that mimic the biological activity of NO, NO mimetics, will bypass cholinergic receptor activation and are anticipated to provide multiple pathways of treating and circumventing dementia in Alzheimer's disease. Activation of soluble guanylyl cyclase and cGMP formation in the brain represents one element of effective neuroprotective pathways mediated by NO. Substantial evidence suggests that NO mimetics may display cGMP-dependent and cGMP-independent activity and may operate via multiple biochemical signaling pathways, both to ensure the survival of neurons subjected to stress and also to provide cognition-enabling pathways to circumvent dementia. GT 1061 is an NO mimetic compound currently in clinical trials for Alzheimer's. A survey of current research indicates that NO mimetics will provide a combined neuroprotective and cognition-enabling approach to anti-neurodegenerative therapy.

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Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain

Cited by 74 publications

References 29 publications

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Differential expression of NO-sensitive guanylyl cyclase subunits during the development of rat cerebellar granule cells: regulation viaN-methyl-D-aspartate receptors

Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

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