The role of phosphodiesterase isoforms 2, 5, and 9 in the regulation of NO-dependent and NO-independent cGMP production in the rat cervical spinal cord

Vente, Jan de; Ittersum, Marjanne Markerink‐van; Vles, Johan S.H.

doi:10.1016/j.jchemneu.2006.02.006

Cited by 29 publications

(11 citation statements)

References 107 publications

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“…The intracellular level of cGMP is controlled by its rate of synthesis via guanylyl cyclases and/or by the rate of its degradation via PDE. 11,26 Serum NO levels in the current study were increased by tadalafil compared with the non-treatment group (p < 0.05) ( Table 2). The tissue NO levels were higher in the tadalafil group compared with the methylprednisolone and non-treatment groups (p < 0.05).…”

Section: Discussionmentioning

confidence: 53%

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Protective effects of tadalafil on experimental spinal cord injury in rats

Serarslan

Yönden

Özgiray

et al. 2010

Journal of Clinical Neuroscience

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Section: Discussionmentioning

confidence: 53%

“…9,10 PDE5 is also found in the spinal cord. 11 A short-acting PDE5 inhibitor (sildenafil) is reported to provide protection against transient spinal cord ischemia in an experimental transient spinal cord ischemia model. 12 Traumatic SCI can precipitate biochemical events that result in functional deficits.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of tadalafil on experimental spinal cord injury in rats

Serarslan

Yönden

Özgiray

et al. 2010

Journal of Clinical Neuroscience

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“…It has been suggested to function as a "housekeeping" PDE to maintain low cellular cGMP (van . PDE9 expression has been reported in retinal pigment epithelial cells and in certain neurons (Diederen et al, 2007;de Vente et al, 2006;ReyesIrisarri et al, 2007). In some instances, its expression in neural tissues coincides with that of the NO-GC; consequently, it has been suggested to play a role in NO/ cGMP signaling in these cells.…”

Section: Isoenzymementioning

confidence: 99%

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

2010

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“…Therapeutic modulation of cGMP has been proposed as a clinical approach to memory deficits (Prickaerts et al, 2002aBoess et al, 2004;Puzzo et al, 2005Puzzo et al, , 2006Puzzo et al, , 2008Puzzo et al, , 2009de Vente et al, 2006;van der Staay et al, 2008). Early studies used nonselective cGMP PDE inhibitors such as zaprinast, later progressing to selective PDE5 inhibitors such as sildenafil (Puzzo et al, 2008(Puzzo et al, , 2009) and PDE9A inhibitors such as BAY 73-6991 to demonstrate improvements in rodent learning and memory models as well as enhanced LTP in hippocampal slices from aged animals (van der Staay et al, 2008).…”

Section: Downloaded Frommentioning

confidence: 99%

Phosphodiesterase 9A Regulates Central cGMP and Modulates Responses to Cholinergic and Monoaminergic Perturbation In Vivo

Kleiman¹,

Chapin²,

Christoffersen³

et al. 2012

J Pharmacol Exp Ther

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Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a highaffinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

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The role of phosphodiesterase isoforms 2, 5, and 9 in the regulation of NO-dependent and NO-independent cGMP production in the rat cervical spinal cord

Cited by 29 publications

References 107 publications

Protective effects of tadalafil on experimental spinal cord injury in rats

Protective effects of tadalafil on experimental spinal cord injury in rats

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

Phosphodiesterase 9A Regulates Central cGMP and Modulates Responses to Cholinergic and Monoaminergic Perturbation In Vivo

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