Phosphodiesterase type 4 that regulates cAMP level in cortical neurons shows high sensitivity to rolipram

Yamashita, Nobuyuki; Yamauchi, Miki; Baba, Jun; Sawa, Aiko

doi:10.1016/s0014-2999(97)01285-5

Cited by 24 publications

(21 citation statements)

References 24 publications

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“…This further confirms that the NMDA effect on cGMP is not due to an indirect effect of cAMP via guanylyl cyclase. Some studies have shown that EHNA increases cGMP in cortical neurons with or without the stimulation of NO-dependent guanylyl cyclase (Yamashita et al, 1997). However, in the present study, it was found that ODQ, an NO-selective guanylyl cyclase inhibitor, blocked the effects of NMDA on cGMP.…”

Section: Discussioncontrasting

confidence: 95%

“…The PDE4 family is the major regulator of cAMP concentrations in many cell types. In cultured cortical neurons, ␤-adrenergic receptor-stimulated cAMP concentrations are predominantly controlled by the PDE4 and PDE2 families (Yamashita et al, 1997). However, in the present study, EHNA, which is a PDE2 inhibitor, did not enhance NMDA receptor-mediated cAMP formation.…”

Section: Discussioncontrasting

confidence: 82%

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Hydrolysis of N-Methyl-d-aspartate Receptor-Stimulated cAMP and cGMP by PDE4 and PDE2 Phosphodiesterases in Primary Neuronal Cultures of Rat Cerebral Cortex and Hippocampus

Suvarna¹,

O'Donnell²

2002

The Journal of Pharmacology and Experimental Therapeutics

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Stimulation of N-methyl-D-aspartate (NMDA) receptors on neurons activates both cAMP and cGMP signaling pathways. Experiments were carried out to determine which phosphodiesterase (PDE) families are involved in the hydrolysis of the cyclic nucleotides formed via this mechanism, using primary neuronal cultures prepared from rat cerebral cortex and hippocampus. The nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) potentiated the ability of NMDA to increase cAMP and cGMP. However, among the family-selective inhibitors, only the PDE4 inhibitor rolipram enhanced the ability of NMDA to increase cAMP in the neurons. In contrast, only the PDE2 inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) enhanced the ability of NMDA to increase cGMP. Neither adenosine nor an adenosine deaminase inhibitor mimicked the effect of EHNA; this suggests that EHNA's inhibition of PDE2, not its effects on adenosine metabolism, mediates its effects on NMDA-stimulated cGMP concentrations. The PDE inhibitoraugmented effects of NMDA on cAMP and cGMP formation were antagonized by 5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801), verifying NMDA receptor mediation. In contrast, only NMDA-mediated cGMP formation was affected by altering either nitric oxide signaling or guanylyl cyclase; this suggests that NMDA-induced changes in cAMP are not secondary to altered cGMP concentrations. Overall, the present findings indicate that cAMP and cGMP formed in neurons as a result of NMDA receptor stimulation are hydrolyzed by PDE4 and PDE2, respectively. Selective inhibitors of the two PDE families will differentially affect the functional consequences of activation of these two signaling pathways by NMDA receptor stimulation.

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Section: Discussioncontrasting

confidence: 95%

Section: Discussioncontrasting

confidence: 82%

Hydrolysis of N-Methyl-d-aspartate Receptor-Stimulated cAMP and cGMP by PDE4 and PDE2 Phosphodiesterases in Primary Neuronal Cultures of Rat Cerebral Cortex and Hippocampus

Suvarna¹,

O'Donnell²

2002

The Journal of Pharmacology and Experimental Therapeutics

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“…Intracellular cAMP level in cortical neurons was increased by approximately 2-fold of basal level by addition of 10 nM isoproterenol as reported (33). Figure 1 represents the augmentation of cAMP level by 4 well-investigated PDE4 inhibitors, rolipram, piclamilast, CDP840, and KF19514, all of which are shown to induce the emetic effect.…”

Section: Enhancement Activity Of Camp Accumulation In Rat Cortical Nesupporting

confidence: 57%

Differential Effects of PDE4 Inhibitors on Cortical Neurons and T-Lymphocytes

Hirose¹,

Manabe²,

Yanagawa³

et al. 2008

J Pharmacol Sci

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“…Actinomycin D was reconstituted in DMSO and added to medium 1 h before NRG1 treatment. All pharmacological treatment was conducted based on previously reported protocols (39)(40)(41)(42).…”

Section: Methodsmentioning

confidence: 99%

Disrupted-in-Schizophrenia-1 expression is regulated by β-site amyloid precursor protein cleaving enzyme-1–neuregulin cascade

Seshadri¹,

Kamiya²,

Yokota

et al. 2010

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

106

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Neuregulin-1 (NRG1) and Disrupted-in-Schizophrenia-1 (DISC1) are promising susceptibility factors for schizophrenia. Both are multifunctional proteins with roles in a variety of neurodevelopmental processes, including progenitor cell proliferation, migration, and differentiation. Here, we provide evidence linking these factors together in a single pathway, which is mediated by ErbB receptors and PI3K/Akt. We show that signaling by NRG1 and NRG2, but not NRG3, increase expression of an isoform of DISC1 in vitro. Receptors ErbB2 and ErbB3, but not ErbB4, are responsible for transducing this effect, and PI3K/Akt signaling is also required. In NRG1 knockout mice, this DISC1 isoform is selectively reduced during neurodevelopment. Furthermore, a similar decrease in DISC1 expression is seen in β-site amyloid precursor protein cleaving enzyme-1 (BACE1) knockout mice, in which NRG1/Akt signaling is reportedly impaired. In contrast to neuronal DISC1 that was reported and characterized, expression of DISC1 in other types of cells in the brain has not been addressed. Here we demonstrate that DISC1, like NRG and ErbB proteins, is expressed in neurons, astrocytes, oligodendrocytes, microglia, and radial progenitors. These findings may connect NRG1, ErbBs, Akt, and DISC1 in a common pathway, which may regulate neurodevelopment and contribute to susceptibility to schizophrenia.

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Phosphodiesterase type 4 that regulates cAMP level in cortical neurons shows high sensitivity to rolipram

Cited by 24 publications

References 24 publications

Hydrolysis of N-Methyl-d-aspartate Receptor-Stimulated cAMP and cGMP by PDE4 and PDE2 Phosphodiesterases in Primary Neuronal Cultures of Rat Cerebral Cortex and Hippocampus

Hydrolysis of N-Methyl-d-aspartate Receptor-Stimulated cAMP and cGMP by PDE4 and PDE2 Phosphodiesterases in Primary Neuronal Cultures of Rat Cerebral Cortex and Hippocampus

Differential Effects of PDE4 Inhibitors on Cortical Neurons and T-Lymphocytes

Disrupted-in-Schizophrenia-1 expression is regulated by β-site amyloid precursor protein cleaving enzyme-1–neuregulin cascade

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